bluuebunny/crossref_metadata_2025 huggingface dataset:
Dancing in the Heart of Organellar Proteomes
Authors: Ping Peipei
Published: April 2024

The rapid development of high accuracy and high sensitivity mass spectrometry technologies has revolutionized our understanding of proteins and their contribution to cellular function. However, there is an increasingly apparent disconnect between these state-of-the-art tools and their effective applications to advance cardiovascular biology and medicine.

Despite progress made in certain areas of investigation, cardiovascular proteomic research faces three major challenges: lack of study designs to accurately pinpoint connections between function and proteomes; limited quantitative information to understand the dynamics of proteomes in disease phenotypes; and the overwhelming quantity and fragmented nature of mass spectra datasets lacking functional annotations. This 2012 Thomas Smith Lecture presentation will provide an overview of the accomplishments in cardiovascular proteomics, highlight the barriers and opportunities in this field, and address the aforementioned obstacles using examples from organellar proteomics investigations, whereby model systems and computational tools are combined to understand human diseases.
Abstract 72: Inhibition of Dynamin Related Protein 1 Mediated Mitochondrial Fission During Cardiac Arrest Is Cardioprotective and Associated with Therapeutic Hypothermia
Authors: Sharp Willard W , Fang Yong Hu , Han Mei , Ryan John , Morrow Erik , Zhang Hannah , Toth Peter , Beiser David , Archer Stephen L
Published: April 2024

Introduction: Mitochondrial fission increases cellular reactive oxygen species (ROS) and apoptosis but its role in cardiac arrest (CA) is unknown. Dynamin related protein 1 (DRP1) enhances fission by translocating to the mitochondria and is regulated by its phosphorylation at Serine 616 (activating) and Serine 637 (inhibiting). We hypothesized that inhibiting fission and DRP1 during CA would be cardioprotective. We also tested whether therapeutic hypothermia (TH) inhibited fission and DRP1.

Methods: Cardiomyocytes isolated from 1-2 day old C57BL6/J mice were infected with a modified baculovirus containing mitochondrial targeted green fluorescent protein and then exposed to simulated ischemia/reperfusion (IR) at 37C or 30C (TH) to assess mitochondrial morphology. Hearts from Sprague Dawley rats were exposed to 30 min of global IR at 37C ± 5 uM mitochondrial inhibitor of division 1 (Mdivi-1) or 30C (TH) in a Langendorff perfusion system. ROS was measured using MitoSOX tissue staining. Left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), DRP1 gene/protein expression, and mitochondrial morphology (electron microscopy) were assessed. Heart samples were also collected from C57BL/6 mice after an 8-min cardiac arrest induced by KCl.

Results: IR increased cell death, mitochondrial fragmentation, ROS, and LVEDP (62±1 mm Hg vs 9±1 mmHg, n=5, p<0.05) while decreasing LVDP (26±11 vs 77±8 mm Hg, p<0.05) compared to perfusion only controls. In IR, DRP1 Serine 637 decreased two-fold (n=4, p<0.05) while total DRP1 in mitochondrial protein fractions increased two fold (n=4, p<.0001). TH and Mdivi-1 maintained mitochondrial morphology, decreased ROS, inhibited DRP1 Serine 637 dephosphorylation and mitochondrial translocation. TH and Mdivi-1 also maintained LVEDP (12±1 and 14±2 mm Hg, n=5) and LVDP (84±6 and 84±2 mm Hg, n=5) at levels similar to perfusion-only controls.

Conclusions: IR is associated with increased mitochondrial fission, DRP1 activation, ROS generation, and contractile dysfunction in cellular and organ models of IR and in vivo CA. Inhibition of fission and DRP1 with Mdivi-1 and TH are cardioprotective. DRP1 may be a therapeutic target for patients suffering CA or undergoing cardiopulmonary bypass.
Abstract 73: Association of Serum Lactate and Survival Outcomes in Patients Undergoing Therapeutic Hypothermia After Cardiac Arrest
Authors: Starodub Roksolana , Abella Benjamin S , Grossestreuer Anne V , Shofer Frances S , Perman Sarah M , Leary Marion , Gaieski David F
Published: April 2024

Introduction
: Recent studies have suggested that serum lactate may serve as a marker to predict mortality after resuscitation from cardiac arrest (CA). The relationship between serum lactate and CA outcomes requires further characterization, especially among patients treated with therapeutic hypothermia (TH) and aggressive post-arrest care.

Methods:
A retrospective analysis of patients resuscitated from non-traumatic CA at three urban U.S. hospitals was performed using an established internet-based post-arrest registry. Adult (≥18 y) patients resuscitated from CA and receiving TH treatment were included. Logistic regression analysis was used to adjust for potential confounders to survival outcomes. Survival to discharge served as the primary endpoint.

Results:
A total of 199 post-CA patients treated with TH between 5/2005 and 11/2011 were included in this analysis. The mean age was 56.9±16.5 years, 85/199 (42.7%) patients were female, and survival to discharge was attained in 84/199 (42.2%). While lower initial post-CA serum lactate levels were not associated with increased survival to discharge, subsequent lactate measurements were significantly associated with outcomes (24-h serum lactate levels in survivors vs non-survivors, 2.7±0.5 vs 4.2±0.4 mmol/L, p<0.01). Multivariable logistic regression confirmed this relationship with survival to discharge (p < 0.01).

Conclusion:
Lower serum lactate levels at 12 h and 24 h, but not initially following cardiac arrest, are associated with survival to hospital discharge after resuscitation from CA and TH treatment. Prospective investigation of serum lactate as a potential prognostic tool in CA is needed.
Abstract 9027: A Novel Polymorphism Arg146 of the Natriuretic Peptide Receptor-3 Gene Results in a Significant Reduction in Protein Expression Due to Accelerated Degradation
Authors: Pereira Naveen , Dong Lin , Pelleymounter Linda , Moon Irene , Stilling Gail , Eckloff Bruce , Wieben Eric , Yee Vivien , Redfield Margaret , Burnett John , Weinshilboum Richard
Published: April 2024

Background: The primary role of natriuretic peptide receptor 3 (NPR3) is clearance of natriuretic peptides. Genetic variation in
NPR3
has been associated with blood pressure regulation and obesity. Despite its importance, variation in
NPR3
characterizing coding single nucleotide polymorphisms (SNPs) has not been addressed by resequencing the gene. Objective: We set out to identify and functionally characterize common variation in
NPR3
in 3 ethnic groups. DNA samples from such subjects are studied because common genetic variation needs to be defined initially in “normal” individuals prior to studying drug effect and response. Also, rare variants identified by sequencing are enriched in complex disease traits.

Methods and Results: DNA samples from 96 European-American, 96 African-American, and 96 Han Chinese-American healthy subjects were used to resequence NPR3. There were 105 polymorphisms identified of which 50 were novel, including 8 nonsynonymous (ns) SNPs of which 7 were novel. Expression constructs for the nsSNPs were created and HEK-293 cells were transfected with constructs for wild type (WT) and the variants. Recombinant proteins were analyzed by quantitative Western blot analysis. A significant reduction in NPR3 immunoreactive protein (60% or less of WT) was observed for the following variants Cys3, Arg146, Val499, and Ser477+Asp521. The Arg146 novel polymorphism resulted in the least protein expression (20% of WT). After treatment of WT and Arg146 cells with proteasome (MG132) and autophagy (3MA) inhibtors, it was determined that autophagy and not proteasomes plays an important role in the degradation of the Arg 146 variant protein. Modeling based on the NPR3 x-ray crystallography structure confirmed that the Arg146 variant were not compatible with WT conformation and could result in protein misfolding or instability.

Conclusions: Multiple novel polymorphisms of NPR3 were identified in 3 ethnic groups. There were 4 variant receptors that displayed a significant decrease in NPR3 protein quantity, Arg146 being the variant with the least expression. Degradation of the variant Arg146 was mediated predominantly by autophagy. This SNP could have a significant effect on the metabolism of natriuretic peptides with clinical implications.
Abstract 9089: Impact of Semiautomated Border Tracking on the Analysis Time and the Accuracy of Right Ventricular Volume Measurements Using DICOM Gradient Cine MR Datasets
Authors: Ashraf Muhammad , Zhu Meihua , Streiff Cole , Sahn David J
Published: April 2024

Background:
Right ventricular (RV) volume measurements on MR images require significant time for tracing multiple short axis planes and is subject to errors due to through plane motion of tricuspid plane, which limits routine clinical application. We tested a new 3D method of RV volume estimation using semiautomated border tracking to reduce both errors and analysis time.

Methods:
We studied 20 latex RV shaped models of different sizes (25-225ml). Each RV model was driven by a calibrated pulsatile pump at 3-5 different stroke volumes (SV, 20-80ml). Motion of the RV model was scanned for gradient cine stacks in multiple short axis, sagittal and coronal planes with a 3T Siemens MR Scanner. Image data was analyzed on an offline RV analysis program embedded in Research Arena VA® (TomTec). Each cine loop was analyzed with manual tracing employing automated border tracking. Datasets were then analyzed for RV volume after manual editing of borders at each short axis level.

Results:
Semiautomated tracking used 3-5 minutes rather than the manual 30-45 minutes. Both methods overestimated ESV and underestimated SV but showed a positive linear correlation (r = 0.80 & 0.87 for ESV and 0.85 & 0.89 for SV respectively) compared to reference values, and good interobserver variability (r = 0.92 & 0.77 respectively). Bland-Altman analysis showed slightly lower bias for manual editing (3.45±0.80) compared to automated tracking (5.25±1.45) but all data points were within 95% confidence intervals.

Conclusions:
The new RVMR program is a user friendly semiautomated program that may be used for clinical assessment of RV volumes.
Abstract 91: Pharmacologically Induced Hypothermia Minimizing Shivering Following Cardiopulmonary Resuscitation
Authors: Chen Wei , Sun Shijie , Weng Yinlun , Tang Wanchun
Published: April 2024

Background: Therapeutic hypothermia reduces oxygen consumption and ischemic injury following successful resuscitation; thereby improves outcomes. However, all the currently available physical cooling techniques cause severe shivering which increases systemic oxygen consumption, and makes it more difficult to maintain target temperature. In this study, we examined the effects of pharmacologically induced hypothermia with WIN 55, 212-2 on shivering during hypothermia in a porcine model of CPR.

Hypothesis: We hypothesized that when WIN55, 212-2 is administered following resuscitation together with surface cooling, it will rapidly reduce the body temperature (BT) without shivering; therefore it is easier to maintain the target temperature.

Methods: Ventricular fibrillation was electrically induced and untreated for 7 mins in 21 male swine weighing 35±2kg. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were randomized to receive the treatment of either WIN 55, 212-2, surface cooling or the combination of WIN55, 212-2 + surface cooling at 5 mins post-resuscitation. The pharmacological cooling was induced by intravenous infused WIN 55, 212-2 (1.0mg/kg/h). The cooling blanket was utilized for surface cooling. The blood temperature, a total dosage of pentobarbital utilization and the incident and duration of shivering during hypothermia were continuously monitored.

Results: During hypothermia, the incident and duration of shivering and the total usage of pentobarbital were significantly reduced in WIN55,212-2 and combination groups when compared with surface cooling group (p<0.001). That was associated with more rapidly decreased blood temperature and easily maintained with 32-34°C in the combination group.

Conclusions: The shivering during hypothermia is minimized by pharmacologically induced hypothermia with WIN 55, 212-2 alone or together with surface cooling. It may provide a new option for inducing hypothermia.
Abstract 9102: Blood Transfusion is Associated with Increased Mortality in Myocardial Infarction-A Meta-analysis and Diversity-Adjusted Study Sequential Analysis
Authors: Chatterjee Saurav , Wetterslev Jorn , Sharma Abhishek , Lichstein Edgar , Wu Wen-Chih , Mukherjee Debabrata
Published: April 2024

Introduction:
The benefit of blood transfusion in patients with myocardial infarction is controversial and harm may be imminent.

Hypothesis:
To identify risk of mortality with blood transfusion in patients with myocardial infarction, through a meta-analysis of published data.

Methods:
A systematic search of studies published between 1966 and March, 2012 was conducted using MEDLINE, EMBASE, CINAHL, Scopus, the Web of Science and Cochrane CENTRAL databases. English-language studies comparing blood transfusion with no transfusion; or a liberal versus restricted transfusion strategy was identified. Two study authors independently reviewed the 729 titles and abstracts originally identified and selected 10 for analysis. Quality of each study was assessed using the strengthening Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. Studies of transfusion strategies in anemia associated with myocardial infarction, and all-cause mortality rates at the longest available follow-up for the individual study, were abstracted. Pooled-effect estimates were calculated with random-effects models.

Results:
Analyses of transfusion in myocardial infarction revealed increased all-cause mortality with a strategy of transfusion during myocardial infarction-18.2% Vs 10.2% [RR 2.91 ( 95% CI 2.46-3.44); p<0.001], with weighted absolute risk increase of 12 %, and a number needed to harm of 8 (95% CI 6-17). However, the mortality risk with transfusion was mitigated when restricted to STEMI patients and those having hematocrit below 30. Multivariate meta-regression revealed that transfusion was associated with higher risk of mortality, independent of baseline hemoglobin, nadir hemoglobin and change in hemoglobin. A higher risk with transfusion compared with no/restrictive transfusion was noted for subsequent myocardial infarction rates too.

Conclusion:
A strategy of blood transfusion/ liberal blood transfusion compared to no/restricted blood transfusion was associated with a higher incidence of all-cause mortality. A practice of routine/liberal blood transfusion in myocardial infarction should not be encouraged but investigated in a large trial with low risk of bias.
Abstract 9248: The Impact of Heart Failure Progression on Post-Left Ventricular Assist Device Survival: An Analysis of the INTERMACS Registry
Authors: Maniar Sanjay , Naftel David , Myers Susan , Topkara Veli K , Novak Eric , Ewald Gregory , Kirklin James K , Mann Douglas L
Published: April 2024

Background:
Proper timing of implantation of continuous flow left ventricular assist devices (CF-LVAD) is an important management decision in patients with advancing heart failure (HF). Previous risk models derived from earlier generation rotary pump devices may not be applicable with CF-VADs. The purpose of this study was to develop a clinically applicable statistical model for predicting 1-year outcomes among patients with progressive HF receiving a CF-LVAD.

Methods:
We analyzed data from all adult primary CF-LVAD (with or without RVAD) patients from June 2006 to December 2010 entered into the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database with 12 months of follow-up (n=2810). Variables entered into the statistical model included patient demographics, pre-implant laboratory data and clinical condition, device strategy, and INTERMACS level (1-7). Parametric proportional hazard analysis was used to identify risk factors for death.

Results:
The significant (p < 0.05) components of the INTERMACS CF-VAD model are illustrated in the Table. As shown, BIVAD support, INTERMACS levels 1 and 2, and prior CABG imparted the highest risk of dying at 1 year. This model also revealed several modifiable risk factors, including BMI, nutritional status, renal and hepatic function, that predicted mortality after CF-VAD implantation. For example, the model predicts that a 10% worsening of renal and hepatic functions in a 45 year old bridge to transplant (BTT) candidate carries ~ 10.9% (13.8% to 15.3%) increased risk of dying at 1 year.

Conclusion:
This risk model allows clinicians to weigh the “cost of waiting” to implant CF-LVADs in patients with advancing HF, and provides a simple method for determining the 1-year mortality in patients with advanced HF receiving a CF-LVAD.
Abstract 9307: Does Preparedness Planning Improve Attitudes and Completion of Advance Directives in Patients with Symptomatic Heart Failure?
Authors: Motie Marjam , Evangelista Lorraine S , Lombardo Dawn , Ballard-Hernandez Jennifer , Malik Shaista , Liao Solomon
Published: April 2024

BACKGROUND:
Limited research exists to support the impact of preparedness planning on attitudes toward and completion of advance directives (ADs) in patients with symptomatic heart failure (HF).

OBJECTIVE:
We conducted this descriptive-correlational study to assess the impact of a palliative care (PC) intervention that facilitates preparedness planning on attitudes and completion of ADs in patients hospitalized for HF exacerbation.

METHODS:
Thirty-six patients (mean age 54 ± 8 years; predominantly male [72%]; White [61%]; married [69%]; New York Heart Association class II [69%]) from single tertiary care facility completed telephone interviews pre- and post-implementation of a PC consultation to facilitate preparedness planning and discussion of patient preferences.

RESULTS:
Mean attitude scores on the Advance Directive Attitude Scale (ADAS) improved from 57 ± 13 at baseline to 80 ± 7 at three months (
P <
.001). Figure 1 illustrates changes in variables of interest over time. Completion of ADs was associated with race, marital status, higher ADAS scores, and better health perceptions at baseline; except for marital status, these associations were also observed post-intervention (Table 1). In addition, knowledge about ADs and discussions related to ADs with family and physicians were associated with completion of ADs post-intervention (all
P
s < 0.05).

CONCLUSION:
A PC consultation enhanced attitudes toward and increased the rate of completion of ADs in patients with symptomatic HF. However, larger scale randomized clinical trials to assess impact of preparedness planning on completion of ADs and outcomes are needed.
Abstract 9349: Asymptomatic Left Ventricular Apical Ballooning as a Potential Risk Factor in Patients with Nontraumatic Subarachnoid Hemorrage
Authors: Mine Takanao , Sato Ikuo , Kishima Hideyuki , Masuyama Tohru
Published: April 2024

Background:
The degree of consciousness impairment at onset in patients(pts) with non-traumatic subarachnoid hemorrhage (NSH) has been found to be closely related to prognosis. Pts with NSH sometimes present with ECG abnormalities or asymptomatic left ventricular apical ballooning (A-LVAB), however risk stratification in pts with NSH still remains unknown. We investigated whether ECG abnormalities and A-LVAB could provide additional risk stratification in patients with NSH.

Methods:
We studied 73 pts (51 females, mean age 69±15 yrs) without a history of heart disease. Neurological grade (Hunt and Kosnik grade) and clinical factors were evaluated. The standard 12-lead ECG and echocardiography were performed within 48 hours after the onset of NSH. ECG abnormalities were defined as abnormal Q wave, ST elevation, ST depression, T-wave inversion, giant T-wave inversion or QT prolongation. We assessed A-LVAB using echocardiography.

Results:
Intervention therapy (clipping 52pts, embolization 11pts) was performed in 63 of 73 patients and 8 of 73 patients (11%) died in the first month after the onset of NSH. A-LVAB was present in 6pts (8%). Death was significantly associated with intervention therapy (p=0.0002), neurological grade (p=0.0003) and A-LVA (p<0.0001), while ECG abnormalities were not significantly associated. Neurological grade (p=0.0326) and A-LVAB (p=0.0107, hazard ratio 39.134, 95%CI 2.341 to 654.185) were independently associated with death.

Conclusion:
Asymptomatic left ventricular apical ballooning could provide additional risk stratification in the acute phase of patients with non-traumatic subarachnoid hemorrhage.
Abstract 9397: Predictors of Disease Progression in Pediatric Dilated Cardiomyopathy
Authors: Molina Kimberly , Sleeper Lynn , Mital Seema , Colan Steven , Shrader Peter , Barker Piers , Margossian Renee , Shirali Girish , Altmann Karen , Canter Charles , Radojewski Elizabeth , Tierney Elif , Rychik Jack , Tani Lloyd
Published: April 2024

Objective:
Identify predictors of disease progression in pediatric dilated cardiomyopathy (DCM).

Methods:
The Pediatric Heart Network Ventricular Volume Variability Study evaluated chronic DCM patients with serial prospective echocardiographic and clinical data collection over an 18 month follow-up. Inclusion criteria were age <22 years and DCM disease duration > 2 months with exclusion of those needing IV inotropic or mechanical support, and those listed status 1A/1B for transplant. Disease progression was defined as an increase in transplant listing status, hospitalization for heart failure, IV inotropes, mechanical support, or death during follow-up. Predictors of disease progression were identified using logistic regression and classification and regression tree (CART) analysis.

Results:
Of the 127 patients, 28 (22%) met criteria for disease progression during the 18 month follow-up period. Multivariable analysis (c-statistic=0.90) identified older age at diagnosis (OR=1.16 per yr, p=0.003), larger left ventricular (LV) end-diastolic m-mode dimension z-score (LVEDDz) (OR 1.77, p<0.001) and lower septal peak systolic tissue Doppler velocity z-score (OR=0.68, p=0.04) as independent predictors of disease progression. CART analysis risk-stratified patients for significant disease progression with 89% sensitivity and 94% specificity based on LVEDDz ≥7.7, LV ejection fraction <38.2%, LV inflow propagation velocity (color m-mode) z-score < -0.28, and age at diagnosis ≥ 8.5 months. (Figure 1)

Conclusion:
In pediatric patients with DCM, diagnosis after late infancy and echocardiographic parameters of LV size, systolic and diastolic function were independently associated with disease progression, and may be used to reliably risk stratify DCM patients.
Abstract 9423: Acute Illness is a Risk Factor for Impaired Respiratory Function during Nurse-administered Procedural Sedation and Analgesia in the Cardiac Catheterization Laboratory
Authors: Conway Aaron , Page Karen , Rolley John , Fulbrook Paul
Published: April 2024

Introduction
Impaired respiratory function (IRF) during procedural sedation and analgesia (PSA) poses considerable risk to patient safety as it can lead to inadequate oxygenation and ventilation. Risk factors that can be screened prior to the procedure have not been identified for the cardiac catheterization laboratory (CCL).

Methods
A matched case-control design was used. Clinical information from two hospitals, one public and one private, was abstracted from 573 medical records of those undergoing procedures in a CCL. IRF was defined as SpO2<95% or less than 8 respirations per minute. To control for potential intra-procedural confounders, those who also received nurse-administered PSA were matched based on the type of procedure as well as age and gender. Factors with significance
p
<0.10 on univariate analyses were entered into a backward stepwise conditional logistic regression model.

Results
Nurses administered PSA during 252 procedures (44%). IRF occurred during 8.3% (95%CI=4.9%-11.7%) of these procedures (n=21). The 21 cases were matched with 113 controls. According to the regression model, with each additional indicator of acute illness, patients were nearly two times more likely than their controls to experience impaired respiratory function during nurse-administered PSA in the CCL (Table). Indicators of acute illness included emergency admission, transfer from critical care unit and requiring respiratory or haemodynamic support in the lead up to the procedure.

Conclusion
The finding that patients with acute illness were most likely to have IRF during PSA has considerable face validity as it is probable these patients had underlying conditions impacting on their cardiopulmonary function. This significant risk needs to be addressed in practice. Nurses should be proactive when managing this group of patients, recognising the increased likelihood for respiratory impairment and applying intensive respiratory monitoring.
Abstract 9448: Soluble Fibrin Monomer-Fibrinogen Complex Levels during Oral Anticoagulant Therapy Does Not Predict Subsequent Thromboembolic Events in Patients with Atrial Fibrillation
Authors: Sadanaga Tsuneaki , Mitamura Hideo
Published: April 2024

Introduction:
Atrial fibrillation (AF) is associated with hemostatic abnormality even during oral anticoagulant therapy. We previously reported that elevated D-dimer level predicted thromboembolic events in AF patients during oral anticoagulant therapy. Likewise, we assessed the hypothesis that soluble fibrin monomer-fibrinogen complex (SF) could be used for the prediction of thromboembolic events because it was considered to be a specific molecular marker for the detection of thrombin generation.

Subject and method:
This study is a post hoc analysis of the previously reported cohort. Protocol 1 included 24 patients with permanent AF (77±10 y/o) in whom SF was measured before and after anticoagulant therapy with warfarin. Protocol 2 included 74 AF patients (75±10 y/o) undergoing treatments with warfarin. SF was measured during warfarin therapy and the patients were prospectively followed. The end point were thromboembolic events.

Results:
Protocol1) Anticoagulation with warfarin significantly reduced SF levels (median, interquartile range) from 4.0 (0.0 - 8.8) to 0.0 (0.0 - 2.2) μ g/ml (left). However, SF levels were still elevated (≥3μ g/ml) in 3 (13%) patients. Protocol 2) INR levels at the time of enrollment were 2.0 ± 0.6. No relationship between SF levels and INR levels were observed (p=0.57). SF levels were ≥ 3 µg/ml in 13 (18%) patients. During an average follow-up time of 683±222 days, 8 (10.8%) thromboembolic events occurred. There were 7 thromboembolic events observed among patients with baseline SF levels < 3μ g/ml as compared with one event in those with baseline SF levels ≥3μ g/ml. Kaplan-Meier thromboembolic event free curve showed that elevated SF did not predictsubsequent thromboembolic events (right).

Conclusion:
Warfarin significantly decreased SF levels; however, elevated level of SF during anticoagulant therapy failed to predict thromboembolic events in AF patients.
Abstract 9518: Miscarriage and Risk of Atherosclerosis, A Nationwide Cohort Study of One Million Women
Authors: Ranthe Mattis F , Andersen Elisabeth W , Bundgaard Henning , Wohlfahrt Jan , Melbye Mads , Boyd Heather A
Published: April 2024

Background:
Atherosclerosis might share aetiology with adverse pregnancy events through metabolic and vascular pathology or inflammatory responses. Knowledge on risk of atherosclerotic diseases in women experiencing spontaneous abortion/miscarriage is limited. In this nationwide cohort study we aimed to examine risk of three different atherosclerotic conditions in women who had experienced miscarriage.

Methods:
In Danish registers, we identified women experiencing a miscarriage or giving birth to a live singleton from 1977-2008. Women aged ≥12 years and free of cardiovascular disease were followed for incident cases of myocardial infarction, cerebral infarction and renovascular hypertension. Using Poisson-regression we estimated incidence rate ratios with 95% confidence intervals for these conditions by history of miscarriages.

Results:
In 1,031,279 women followed for more than 15 million person-years, we identified 2,798 incident cases of myocardial infarction, 4,053 incident cerebral infarcts and 1,448 incident cases of renovascular hypertension. Incidence rate ratios with 95% confidence intervals (adjusted for age, calendar-period, and number of children) for one and ≥four miscarriages respectively compared to no miscarrriages, were 1.11 (1.00-1.23) and 2.08 (1.25-3.45) for myocardial infarction, 1.13 (1.03-1.23) and 1.89 (1.20-2.96) for cerebral infarction, and 1.15 (0.99-1.34) and 3.78 (2.08-6.85) for renovascular hypertension. Trends with 95% confidence intervals for step-wise increase in risk for the three conditions given one additional miscarriage was 9% (3-16%), 13% (7-19%) and 19% (9-30%), in those aged ≤32 years all trends rose to around 60%. Adjusting for smoking, diabetes mellitus, polycystic ovarian syndrome and thrombophilia left estimates unchanged. Similar strong and consistent trends were not observed for live birth history.

Conclusion:
We found a consistent association between previous miscarriages and increased risk of myocardial infarction, cerebral infarction and renovascular hypertension. This is suggestive of shared aetiology in atherosclerosis and miscarriage, or possible pathological processes initiated by a miscarriage and leading to atherosclerosis.
Abstract 9521: Ventricular Dyssynchrony at Baseline Predicts Transplant-Free Long-Term Survival in Patients Treated by Cardiac Resynchronization Therapy
Authors: Prinz Christian , Felice Cinthia D , Lehmann Roman , Schwarz Maria , Prinz Eva-Maria , Bitter Thomas , Vogt Júrgen , Horstkotte Dieter , Lamp Barbara , Faber Lothar
Published: April 2024

Aim
s: To analyze whether left ventricular dyssynchrony (LVD) at baseline is predictive for long-term outcome in heart failure (CHF) patients with left ventricular (LV) dysfunction and conduction disturbances treated with cardiac resynchronization therapy (CRT).

Methods: In 504 consecutive individuals with CHF scheduled for implantation of a CRT device, LVD was assessed by tissue Doppler imaging (TDI), defined as an electromechanical delay (EMD) difference of ≥40 ms in 2 opposed left ventricular wall regions (septal vs. lateral, anterior vs. inferior). All-cause mortality, heart transplantation, or assist device implantation was defined as combined primary end point. Secondary end points were measures of reverse LV remodeling and of symptomatic improvement.

Results: Mean follow-up was 68±36 months. LVD at baseline was present in 308 patients (61%). Of these, 24% reached the combined primary endpoint in contrast to 58% of patients without LVD (p<0.001). Furthermore, patients with LVD showed pronounced improvement of all secondary end point parameters. An independent association was found between outcome, LVD (β-coefficient in the final model 0.4, p<0.001), and gender (β-coefficient in the final model 0.2, p=0.002).

Conclusions:
LVD at baseline as assessed by TDI is associated with more pronounced reverse LV remodeling and seems to be a predictor for transplant-free long-term survival in CRT recipients.
Abstract 9574: Enhanced Rho-kinase Activity in Circulating Neutrophils of Patients with Vasospastic Angina after the Great East Japan Earthquake
Authors: Nihei Taro , Takahashi Jun , Kikuchi Yoku , Hao Kiyotaka , Takagi Yusuke , Tsuburaya Ryuji , Shiroto Takashi , Ito Yoshitaka , Matsumoto Yasuharu , Nakayama Masaharu , Ito Kenta , Yasuda Satoshi , Shimokawa Hiroaki
Published: April 2024

Purpose:

We have recently demonstrated that Rho-kinase activity in circulating neutrophils is a useful biomarker for diagnosis and disease activity assessment of vasospastic angina (VSA). Coronary vasospastic activity is known to be enhanced under stressful conditions. On March 11, 2011, we experienced the Great East Japan Earthquake in our Tohoku area. In this study, we thus examined whether Rho-kinase activity was increased in VSA patients after the Earthquake.

Methods:

In 11 patients with proven VSA (M/F 8/3, 62±11 yrs), we were able to measure Rho-kinase activity in circulating neutrophils at 3 time points, before and 6 and 12 months after the Earthquake. Rho-kinase activity was defined by the ratio of phosphorylated form/total form of myosin-binding subunit (MBS), a substrate of Rho-kinase. We also quantitatively examined the extent of mental stress by the post-traumatic stress disorder (PTSD) questionnaire.

Results:

In the VSA patients, Rho-kinase activity was significantly increased at 6 months after the Earthquake despite the continued medical treatment with calcium channel blockers, which was returned to baseline level at 12 months (0.99±0.34 at baseline, 1.71±0.23 at 6 months, and 0.90±0.34 at 12 months) (
Figure
). Among the 11 patients, 3 patients were directly hit by the Tsunami, who complained increased frequency of angina attacks and the use of sublingual nitroglycerin after the Earthquake. Importantly, in those 3 patients, as compared with the remaining 8 patients without direct tsunami hit or changes in symptoms, both PTSD score (32±7 vs. 5±8, P=0.01) and the changes in Rho-kinase activity at 6 months from the baseline (268±232% vs. 55±40%, P<0.05) were significantly higher. Furthermore, there was a significant correlation between the Rho-kinase activity changes and the PTSD score (r= 0.67, P<0.05).

Conclusions:

These results indicate that Rho-kinase activity of VSA patients was transiently enhanced by the disaster-related mental stress.
Abstract 9607: Development of Microporous Covered Stents for Treating Cerebral Aneurysms with Maintenance of Branching Flow
Authors: Nakayama Yasuhide , Nishi Shogo , Ishibashi-Ueda Hatsue
Published: April 2024

Objective:
Treatment of large (diameter: 12~25 mm) or giant (diameter: over 25 mm) cerebral aneurysms with broad neck in the cranio-cervical area is extremely difficult or carries high risks, even with clinical available surgical method or endovascular one using coils with the assistance of bare stents. In this study, we developed a novel balloon-expandable, microporous covered stent for treating such intractable cerebral aneurysms with high safety and reliability.

Methods and Results:
The covered stents were prepared using the specially designed balloon-expandable stents with open cell structure (CoCr, Japan Stent Technology; 3 mm x 20 mm). The stents had thin polyurethane cover membrane (thickness: 20 μ m), in which strut was completely impregnated, with a larger amount of micropores (diameter: 100~300 μ m, opening ratio: 10~30%). The experimental aneurysms (10~15 mm) were created at rabbit brachiocephalic arteries (3 mm) by distal ligation and intraluminal elastase incubation at right common carotid arteries. Upon placing the covered stents at the neck of the aneurysms all aneurysms were occluded immediately (n=15), whereas remaining of the aneurysms was occurred by bare stents even after 6 months (n=5). All the parent arteries were patent after implantation up to 12 months. At 3 months of implantation inner space of the aneurysms was filled completely with granulomatous tissue and luminal surface was covered with extremely thin neointima (n=5, thickness; 68 ± 22 μ m). The branching flow through the cover membrane was maintained in all cases.

Conclusion:
The newly developed covered stents performed well in terms of creating less intimal hyperplasia with maximum embolization effect without disturbing branching flow.
Abstract 9608: Intracoronary Administration of Nicorandil During Direct Coronary Stenting Complements Restoration of Regional Perfusion at Subacute Phase of Myocardial Infarction: A Demonstration With O-15 Water Pet
Authors: Takabatake Wataru , Iwado Yasuyoshi , Ishikawa Kaori , Miyauchi Yuka , Tada Kumi , Murakami Kazushi , Noma Takahisa , Ohmori Koji , Nisiyama Yosihiro , Kohno Masakazu
Published: April 2024

Purpose:
Controversies exist regarding the impact of nicorandil as the adjunctive therapy for direct coronary stenting in patients with ST elevation myocardial infarction (STEMI).Therefore, we performed O-15 water positron emission tomography (water PET) to quantify regional myocardial perfusion in patients with STEMI who received nicorandil or no adjunctive therapy during successful direct stenting.

Methods:
In 28 patients with STEMI (65+/-13 yrs: 22 males), direct stenting was performed within 8 hrs after the onset. Five of 28 patients who underwent successful direct stenting received intracoronary administration (i.c.) of nicorandil 4 mg immediately after the first recanalization of culprit lesion.At 3 to 4 weeks from the onset, water PET was performed in which myocardial blood flow (MBF) was measured at rest and during hyperemia and myocardial vascular esistance (MVR) was calculated. Data were obtained from both reperfused and normal control regions in each patient.

Results:
See Figure. In patients who did not receive nicorandil (No-Nico), MBF in reperfused area (Rep) was lower than that in normal control regions (Cont) both at rest and during hyperemia (ATP). However, in the nicorandil-treated patients, MBF in Rep was restored to the similar level of that in Cont both at rest and during ATP. MVR was elevated in Rep both at rest and during ATP in No-Nico patients; such elevation of MVR in Rep was successfully prevented in the nicorandil-treated patients.

Conclusion:
O-15 water-PET at subacute phase revealed that i.c.nicorandil during direct stenting successfully prevented the elevation of myocardial vascular resistance and thus, restored myocardial blood flow in reperfused areas to the similar level as that in non-infarcted regions in patients with STEMI.
Abstract 9615: Longitudinal Strain as a Novel Predictor of All-cause and Cardiovascular Mortality in Asymptomatic Hemodialysis Patients with Preserved Left Ventricular Ejection Fraction
Authors: Liu Yen-Wen
Published: April 2024

Background
End-stage renal disease is notorious for high mortality. For asymptomatic hemodialysis patients with preserved left ventricular ejection fraction (LVEF), little is known regarding the prognostic predictors. Two-dimensional speckle-tracking echocardiography with myocardial deformation analysis (2D strain) is reliable to assess LV function accurately and objectively. The prospective study was conducted to investigate prognostic value of LV global peak systolic longitudinal strain (GLS) in asymptomatic hemodialysis patients with preserved LVEF.

Methods
Asymptomatic hemodialysis patients with LVEF≥50% underwent biochemistry blood tests, echocardiography, and 2D strain analysis. These patients were followed-up for more than 2.5 years.

Results
Lower albumin levels, deteriorated GLS, and higher cardiac troponin T (cTnT) levels were detected in the mortality group compared to the controls. In Cox regression model, reduced GLS (GLS≥-15%, Hazard ratio (HR): 1.26,
p
=0.002) and increased cTnT level (cTnT >0.03 ng/ml, log cTnT HR: 14.43,
p
<0.001) were predictors to all-cause mortality (Figure A and B). Furthermore, hemodialysis patients with reduced GLS, but not those with increased cTnT level, had higher cardiovascular mortality rate (Figure C and D). Patients with cTnT >0.03 ng/ml and GLS ≥-15% had 7.8 times the risk of all-cause mortality and 6.1 times the risk of cardiovascular death compared to those with cTnT ≤0.03 ng/ml and GLS <-15%.

Conclusions
Among asymptomatic hemodialysis patients with preserved LVEF, increased cTnT level and reduced GLS were associated with worse prognosis. Compared to cTnT, GLS is a stronger prognostic indicator in asymptomatic hemodialysis patients. The incremental prognostic value of GLS with elevated cTnT is potentially efficient and reliable.
Abstract 9628: Association of Electrogram Features and Critical Reentrant Ventricular Tachycardia Sites with Nonischemic Scar on Late Gadolinium Enhanced Cardiac Magnetic Resonance
Authors: Sasaki Takeshi , Sasaki Takeshi , Miller Christopher F , Hansford Rozann , Zviman Menekhem M , Marine Joseph E , Spragg David , Cheng Alan , Tandri Harikrishna , Sinha Sunil , Kolandaivelu Aravindan , Zimmerman Stefan L , Bluemke David A , Tomaselli Gordon F , Berger Ronald D , Halperin Henry R , Calkins Hugh , Nazarian Saman
Published: April 2024

Introductions:
The association of local electrogram features with nonischemic scar morphology and distribution on electroanatomic maps (EAM) has not been investigated. We aimed to quantitatively assess the association of nonischemic scar on late-gadolinium enhanced cardiac magnetic resonance (LGE-CMR) with local electrograms and critical sites in patients with nonischemic cardiomyopathy (NICM).

Methods:
LGE-CMR was performed in 19 patients with NICM. Scar characteristics were classified by scar transmurality and intramural scar types (endocardial, mid-wall, epicardial, patchy, transmural) on LGE-CMR short-axis planes (Figure, upper panel). EAM points were registered to the corresponding LGE-CMR images. Multivariable regression analysis clustered by patient was performed to assess the association of myocardium thickness, scar transmurality and intramural scar types, with electrogram bipolar/unipolar amplitude, duration and deflections. LGE-CMR characteristics of critical ventricular tachycardia (VT) sites were also investigated.

Results:
In pooled analyses, higher scar transmurality was significantly associated with lower bipolar (Figure, lower panel)and unipolar electrogram amplitude, longer duration and more deflections (P<0.0001). Fractionated and isolated potentials were more likely to be observed in regions with higher scar transmurality (P<0.0001) and patchy scar (vs. endocardial, mid-wall, epicardial scar, P<0.05). Most of the critical sites (16 sites; 89%) were located in scar with >25% scar transmurality. Myocardial wall thickness, scar transmurality and intramural scar types were independently associated with electrogram features on multivariable regression analyses.

Conclusions:
Electrogram features on endocardial EAM are associated with scar morphology and distribution on LGE-CMR in NICM. This result may optimize procedural strategies including the decision to obtain epicardial access.
Abstract 9639: Pre-Transplant Circulating Antibodies Predict Development of Antibody-Mediated Rejection after Heart Transplant Using the New ISHLT Antibody-Mediated Rejection Pathology Grading Scale
Authors: Kittleson Michelle , Patel Jignesh , Rafiei Matthew , Hage Antoine , Stern Lily , Esmailian Fardad , Reinsmoen Nancy , Kobashigawa Jon
Published: April 2024

Purpose:
Pre-transplant circulating antibodies have been associated with the development of antibody mediated rejection (AMR) following heart transplantation. The new pathology antibody mediated rejection scale was developed in 2009 and now the diagnosis of antibody mediated rejection is standardized through this pathology scale. We chose to assess whether pre-transplant circulating antibodies do indeed lead to more pathology antibody mediated rejection according to the new International Society for Heart and Lung Transplantation (ISHLT) AMR grading scale.

Methods:
Between January 1, 2010 and July 1, 2011 we evaluated 106 heart transplant recipients for their pre-transplant percentages of peak panel reactive antibody (PRA). Patients were divided into the following subgroups depending on the percentage of peak pre-transplant PRA: peak PRA 0-9% (n = 67), PRA ≥ 10% (n = 39), PRA ≥ 25% (n = 31), PRA ≥ 50% (n = 25), PRA ≥ 75% (n = 19), and PRA = 100% (n = 4). The endpoints of this study were first-year pathology antibody mediated rejection and treated antibody mediated rejection. Treated antibody mediated rejection was mainly due to symptoms of heart failure and or decrease in left ventricular ejection fraction.

Results:
Patients with higher pre-transplant PRA's had significantly more pathology antibody mediated rejection in the first-year after heart transplantation compared to patients with a peak PRA 0-9% (see table). The number of treated antibody mediated rejection episodes also increased with higher PRA's, which were also significantly different from the peak PRA 0-9% group.

Conclusion:
Pre-transplant circulating antibodies appear to predict pathology antibody mediated rejection according to the most recent ISHLT grading scale. This appears to confirm that pre-transplant circulating antibodies greater than 10% is a threshold for antibody-mediated rejection and therefore consideration for augmentation of immunosuppression should be considered.
Abstract 9642: Prolongation of AERP and APD with the Selective IKur inhibitor, BMS-394136, is Increased in the Zucker Diabetic Fatty Rat
Authors: Xing Dezhi , Zhu Jialong , Hennan James K , Levesque Paul C
Published: April 2024

Introduction:
Diabeties mellitus is a risk factor for atrial fibrillation (AF). We previously reported that atrial ischemia increases activity of a selective IKur inhibitor, BMS-394136, on atrial effective refractory period (AERP) and action potential duration (APD) without effecting ventricular effective refractory period (VERP) in dog heart. This study evaluated the efficacy of BMS-394136 on AERP and APD in Zucker Diabetic Fatty (ZDF) rats.

Methods:
Male ZDF370 (obese and diabetic) and ZDF371 (lean control) rats on normal diet, averaging 7 months of age, were entered into the study. After induction of anesthesia, a 2F multielectrode was placed into right ventricle to measure VERP. BMS-394136 (10 mg/kg) was infused over 5 min through the jugular vein. After VERP assessment, hearts were removed and perfused in a Langendorff apparatus with Tyrode’s buffer for assessment of AERP and APD at BMS-394136 concentrations of 1.0, 3.0 and 10.0 µM, respectively. After Langendorff perfusion, atrial strips were removed and studied with standard microelectrode techniques in perfusion.

Results:
(*p<0.05). The average weight and blood glucose was 367g and >600mg/dl in the ZDF370 rats and 465g* and 253* mg/dl in the ZDF371 rats. VERP was prolonged by BMS-394136 in vivo by 21±1.7 ms (39%) in ZDF370 rats (n=10), and by 24±1.7 ms (50%) in ZDF371 rats. No differences in APD100 (64±4ms vs 64±3 ms) or AERP (29±2ms vs 25±2ms) were observed at baseline in Langendorff mode from ZDF370 and ZDF371 hearts (n=4/each). However, BMS-394136 dose-dependently prolonged APD100 and AERP to a greater extent in ZDF370 rats at 1.0µM (11%* and 36%*), 3.0µM (27%* and 44%*) and 10.0µM (33%* and 64%*) than in ZDF371 rats at 1.0µM (-2%* and 3%), 3.0µM (3% and 3%) and 10.0 µM (8% and 14%). In atrial strips (n=4), BMS-394136 increased APD30 by (%) 0±2, 22±3, 33±2*, APD50 by(%) 14±4, 36±5, 32±7, 50±4* and APD90 by (%)3±4, 14±9, 23±5* at concentrations of 1.0µM, 3.0µM and 10.0 μ M in ZDF370 rats, no effect was observed on APD prolongation in ZDF371 rats.

Conclusions:
Diabeties mellitus may increase the efficacy of the selective IKur inhibitor, BMS-394136, on prolongation of AERP and APD. The absence of effect with BMS-394136 on VERP confirms the atrial selective activity of this compound or ion channel remodeling.