bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9292: Impact of Nicorandil on Infarct Myocardium in Comparison With Nitrate: Assessed by Cardiac Magnetic Resonance Imaging
Authors: Yamada Kiyoyasu , Isobe Satoshi , Yokouchi Kazuhiko , Iwata Hirokazu
Published: April 2024

Objectives
The complementary intravenous administration of nicorandil, a hybrid compound of ATP-sensitive potassium channel opener and nitric donor, to percutaneous coronary intervention (PCI) reportedly has a protective effect on the infarct myocardium, leading to improve clinical outcome in patients with acute myocardial infarction (AMI). We compared the infarct and edema size in AMI patients intravenously treated by nicorandil with those by nitrate, using cardiac magnetic resonance (CMR) imaging.

Methods
The double-blinded trial was conducted in 52 AMI patients who successfully underwent emergency PCI. The patients were assigned to receive nicorandil or nitrate just before reperfusion at random. For the assessment of infarct and edema areas, short-axis T2w and delayed enhancement (DE) CMR images were acquired 6.1 ± 2.4 days after the onset of AMI.

Results
The edema size on T2w CMR was significantly larger than the infarct size on DE CMR (p < 0.05). A significant correlation was observed between the peak creatine kinase (CK) levels and infarct size on DE CMR (r = 0.62, p < 0.05) as well as the edema size on T2w CMR (r = 0.7, p < 0.05) in patients treated by nicorandil. A similar correlation was seen between the peak CK levels and infarct size on DE CMR (r = 0.84, p < 0.05) as well as the edema size on T2w CMR (r = 0.84, p < 0.05) in patients treated by nitrate. The maximum serum CK level was significantly lower in patients treated by nicorandil than those by nitrate (2132 ± 1689 IU. vs 2785 ± 2121 IU. ; p < 0.05). Both the edema size on T2w CMR and the infarct size on DE CMR were significantly smaller in patients treated by nicorandil than those by nitrate (edema size; 17.7 ± 9.9 % vs 21.9 ± 13.7 % ; infarct size; 10.3 ± 6.0 % vs 12.7 ± 6.9 % ; p < 0.05, respectively).

Conclusion
Using CMR imaging, we demonstrate that the complementary intravenous administration of nicorandil to PCI provides more favorable effects in reducing myocardial damage compared with nitrate.
Abstract 9301: The Comparison of Warfarin and Dabigatran in the Incidence of Asymptomatic Cerebral Micro Thromboembolism after AF Ablation
Authors: Ichiki Hitoshi , Oketani Naoya , Iriki Yasuhisa , Okui Hideki , Maenosono Ryuichi , Namino Fuminori , Ishida Sanemasa , Ninomiya Yuichi , Matsushita Takehiko , Hamasaki Shuichi , Tei Chuwa
Published: April 2024

Background:
Asymptomatic cerebral thromboembolism after atrial fibrillation (AF) ablation has been reported in 4-20% of the patients. Uninterrupted anticoagulation therapy using warfarin has been shown to be effective for preventing perioperative cerebral thromboembolism without increasing the bleeding complications. Dabigatran, a new anticoagulation agent, has been reported the comparable effects for preventing symptomatic thromboembolic events in non-valvular AF patients. Thus we investigated the incidence of asymptomatic cerebral thromboembolism after AF ablation with dabigatran compared with warfarin using diffusion- and T2-weighted magnetic resonance imaging (DW/T2-MRI).

Methods:
This study was a prospective non-randomized observational study included 210 consecutive patients (112 paroxysmal AF) who underwent AF ablation solely guided by complex fractionated atrial electrograms (n=113) or combined with PVI (n=97). Warfarin was used for perioperative anticoagulation therapy in 180 patients (warfarin group), and dabigatran was used in 30 patients (dabigatran group). Warfarin was not discontinued for the procedure, whereas dabigatran was not prescribed in the morning of the procedure. Irrigation catheters with the maximum power of 40 watts were used in all the cases. All the patients underwent cerebral DW/T2-MRI in the day after ablation.

Results:
The incidence of asymptomatic cerebral thromboembolism and hemopericardium treated with pericardiocentesis was higher in dabigatran group than in warfarin group [20.0% vs 7.8% (P<0.05), 13.3% vs 2.2% (P<0.05), respectively]. Although left atrial (LA) diameter and left ventricular (LV) mass were smaller in dabigatran group than in warfarin group [40+9 mm vs 43+7 mm (P<0.05), 189.6+53.0 g vs 161.9+34.8 g (P<0.05), respectively], there was no significantly difference in age, CHADS2 score, the proportion of paroxysmal/persistent AF, LA appendage flow speed, LV ejection fraction, mean activated coagulation time during the procedure, and radiofrequency time between the both groups.

Conclusion:
Perioperative uninterrupted anticoagulation therapy using warfarin was safer and more effective compared with dabigatran for catheter ablation of AF.
Abstract 9310: Gender and Outcomes Following Primary Prevention ICD Placement: Analysis of the NCDR ICD Registry
Authors: Russo Andrea M , Daugherty Stacie L , Masoudi Frederick A , Wang Yongfei , Mazzarelli Joanne , Curtis Jeptha , Lampert Rachel
Published: April 2024

Background:

Due to the small numbers of women enrolled in implantable cardioverter defibrillator (ICD) trials, outcome for women has not been well-described. This study compares intermediate-term outcomes in a large cohort of men and women receiving single or dual chamber ICDs for primary prevention.

Methods:

38,912 initial implants (25% women) with single or dual chamber ICDs for primary prevention between 2006 and 2009 in the NCDR ICD Registry were identified. Baseline characteristics and outcomes, including complications, six-month heart failure (HF) readmission, and six-month mortality were compared between men and women using chi-square tests for categorical variables and unbalanced t-tests for continuous variables. Complications were considered within 30 or 90 days of implantation, including pneumothorax requiring chest tube, hematoma requiring transfusion or evacuation, tamponade, or death within 30 days, or mechanical complications with system revision, device-related infection, or post-index ICD within 90 days. The differences in outcomes between genders were also examined through multivariable logistic regression models adjusting for possible confounders.

Results:

Differences in baseline characteristics and drug therapy were noted between men and women (Table). Complications at 30 or 90 days, 6-month mortality, and 6-month HF readmission were significantly more frequent in women (p<0.001 for all). Differences in complications or mortality (OR 1.40, 95% CI 1.27,1.54, p<0.001), or HF readmission (OR 1.34, 95% CI 1.25, 1.44, p<0.001) persisted after adjusting for differences in baseline characteristics and device type.

Conclusions:

Following ICD implantation for primary prevention indications, complication rates, six-month HF readmission rates, and six-month mortality rates are higher in women than men. Whether these gender differences in outcome impact the benefit of ICDs in women requires further investigation.
Abstract 9355: Mitral Valve Disease in Marfan Syndrome Patients Undergoing Aortic Root Replacement
Authors: Kunkala Meghana , Schaff Hartzell , Li Zhou , Volguina Irina , LeMaire Scott A , Coselli Joseph , Connolly Heidi
Published: April 2024

Background:
The primary cardiac manifestations of the Marfan syndrome (MFS) include aortic root dilation and mitral valve prolapse (MVP). There are only scant data describing MV disease in MFS patients who undergo aortic root replacement.

Methods:
We retrospectively studied 239 patients (90 female; mean age 34 y) with MFS enrolled in a prospective multicenter registry. All patients were referred for repair of aortic root aneurysms with either composite graft aortic valve replacement (AVR, n=59) or an aortic valve-sparing procedure (AVS, n=180). MVP and mitral regurgitation (MR) severity was evaluated by echocardiography preoperatively and during follow-up (postoperatively, 6 months, and 1, 2, and 3 years after surgery). The severity of MR was graded as none, trivial (0), mild (1), moderate (2), moderate to severe (3), or severe (4). Preoperative echocardiography identified MVP in 166 (69%) patients without previous MV intervention.

Results:
Forty-one (25%) of 166 patients with MVP received AVR, and 125 (75%) received AVS, with similar proportions of patients with preoperative MR grade >2 in the two groups (
p
=0.7). Thirty-three patients (20%) underwent concomitant MV intervention: 29 repairs and 4 replacements (15 patients (45%) had MR >2, 11 (33%) had MR=2, and 7 had MR ≤1). All patients with MR >2 underwent a MV procedure. One patient following MV repair required MV replacement on postoperative day 16 after developing grade 4 MR. No other patient required MV reintervention during follow-up (mean clinical follow-up, 30±9 months). Echocardiography performed 21±13 (±1 SD) months postoperatively revealed MR >2 in only 1 of 158 patients. There were 1 early death (bleeding) and 2 late deaths (multi-organ failure and unknown cause); all deaths occurred in patients with concomitant MV surgery.

Conclusions:
MVP is present in 69% of patients with MFS undergoing aortic root replacement; 20% of patients with MVP underwent a concomitant MV procedure. Short-term results suggest that a simultaneous MV procedure in patients with MR >2 is reasonable because operative risk was not increased and subsequent MV procedures were rare. More follow-up is needed to learn if prophylactic MV intervention at the time of aortic surgery might benefit patients with MR ≤2.
Abstract 9374: Zinc Finger Nuclease Technology for Human Pluripotent Stem Cell Genomic Modification and
In Vivo
Tracking
Authors: Zhang Wendy Y , Wang Yongming , Hu Shijun , Lan Feng , Wu Joseph C
Published: April 2024

INTRODUCTION & HYPOTHESIS:
Heart disease is the leading cause of death in developed nations and remains a significant public health problem both in the United States and globally. Human embryonic stem cell therapy demonstrates to be an effective means of treating ischemic heart diseases, as it possesses the capability of generating
de novo
tissue populations. To investigate such populations’
in vivo
and
in vitro
behavioral characteristics as well as clinical potentials, molecular imaging proves to be a vital tool. However, thus far, genetic integration mainly relies upon the unsafe, unstable, and untranslatable method of random integration. We hypothesized that to address such barrier, we can utilize novel zinc finger nuclease (ZFN) technology to integrate reporter genes into human pluripotent stem cells for cardiac cell derivation, delivery, and molecular imaging.

METHODS & RESULTS:
Using ZFN technology, we integrated a triple fusion gene construct of mRFP-Fluc-HSVtk into the safe AAVS1 locus for fluorescence, bioluminescence, and positron emission tomography imaging. No discernible off-target cleavages or random integration was detected, and we achieved a high efficiency of ZFN-mediated targeted integration. We observed long-term reporter gene expression as well as pluripotency conservation; the cells retained both expression of pluripotency markers - Oct4, Tra-1-60, Sox2, Tra-1-81, Nanog and SSEA4 - as wells as ability to differentiate into 3 germ layers via
in vivo
teratoma formation and
in vitro
embryoid body formation. We then differentiated the ZFN-modified ESCs into cardiomyocytes and endothelial cells
in vitro
. Parallel characterization of differentiation efficiency and cardiac marker expression of ZFN-modified ESCs and blank ESCs showed no significant differences between the two. Functionally, we tracked the survival of ZFN-edited pluripotent cells in murine models, demonstrating the cardiovascular applicability of ZFN-edited cells.

CONCLUSION:
This study demonstrates the great potentials and applicability of ZFN transgenesis technology use in safe, stable, and effective genetic integration for the molecular imaging of human pluripotent stem cells and beyond.
Abstract 9419: A Novel Global Strain Imaging Diastolic Index for the Estimation of Left Ventricular Filling Pressure
Authors: Chiang Shuo-Ju , Daimon Masao , Ishii Katsuhisa , Hirose Kuniaki , Kawata Takayuki , Miyauchi Katsumi , Yah Mei-Hsiu , Chang Nen-Chung , Daida Hiroyuki
Published: April 2024

Background:
Recently, strain imaging diastolic index (SIDI) has been proposed to assess left ventricular (LV) regional abnormal relaxation induced by myocardial ischemia. We aimed to examine whether non-invasive global SIDI obtained using 2D speckle tracking imaging (2DSI) could predict elevated levels of LV filling pressure.

Methods:
One hundred and twenty patients (age
63±13
years) with suspected coronary artery disease underwent echocardiography and 2DSI during simultaneous cardiac catheterization. Mean LV ejection fraction was 46.3±17.6%. LV pressure curve was obtained to measure pre-atrial contraction (Pre-AC) pressure as a surrogate for LV filling pressure. SI-DI was defined as LV longitudinal changes during the first one-third of diastolic duration. In 2DSI, LV longitudinal SIDI of 18 LV segments were measured from the apical 2-, 3-, and 4-chamber views. Then, longitudinal global SIDI (L-global SIDI) was calculated as a mean SIDI of 18 LV segments. Mitral inflow and tissue Doppler imaging were also assessed.

Results:
Among 120 patients, 64 cases had Pre-AC pressure > 15 mmHg. L-global SIDI had a significant and better correlation with pre-AC pressure (p<0.001, R=0.47)(Figure 1), than E/e’ (p<0.01, R=0.26) . In multiple stepwise regression analysis, L-global SIDI was the strongest independent determinant of pre-AC pressure (β=-0.66, P<0.001), among E/A, left atrium volume index, E/e’, and e’. In addition, L-global<0.50 was the optimum cutoff value to predict LV pre-AC pressure >15mmHg (sensitivity, 89%; specificity, 51%)(Figure 2), while E/e’>11.2, the optimum cutoff value of E/e’ predicted LV pre-A contraction pressure >15mmHg (sensitivity, 65%; specificity, 75%).

Conclusions:
L-global SIDI derived from 2DSI can be used to estimate LV filling pressure noninvasively. Global SI-DI may provide more accurate estimation of LV filling pressure, compared with conventional mitral inflow and tissue speckle tracking.
Abstract 9690: CIKS (Act1 Or TRAF3IP2) is Critical in High Glucose-induced Endothelial Dysfunction
Authors: Venkatesan Balachandar , Valente Anthony J , Siebenlist Ulrich , Chandrasekar Bysani
Published: April 2024

Endothelial dysfunction is characterized by enhanced inflammatory cytokine and adhesion molecule expression, and endothelial-monocyte adhesion. The adapter molecule CIKS (connection to IKK and SAPK/JNK; also known as CIKS or TRAF3IP2) mediates NF-κB and AP-1 activation, and plays a role in inflammation and injury. Here we show that the high glucose (HG; 25 mM versus 5 mM D-glucose)-induced increase in endothelial-monocyte adhesion, and inhibition of human primary aortic endothelial cell (EC) migration and proliferation are reversed by CIKS knockdown. HG induced CIKS mRNA and protein expression via DPI-inhibitable Nox4-dependent ROS generation. Further, HG-enhanced CIKS promoter-dependent reporter gene activation was blocked by DPI, knockdown of Nox4, c-Jun or C/EBPβ or mutations in AP-1 or C/EBP binding sites. Interestingly, HG enhanced CIKS nuclear translocation. Coimmunoprecipitation and immunoblotting revealed CIKS/IKKβ/JNK physical association under basal conditions that was enhanced following HG treatment. Importantly, CIKS knockdown reversed HG-induced (i) IKKβ and JNK phosphorylation, (ii) p65 and c-Jun nuclear translocation, (iii) NF-κB- and AP-1-dependent proinflammatory cytokine (IL-18, IL-1β), chemokine (IL-8, MCP-1) and adhesion molecule (ICAM-1, VCAM-1) expression, (iv) endothelial-monocyte adhesion, and (v) inhibition in EC migration and proliferation. Similar to HG, AGE-BSA and ox-LDL markedly increased CIKS expression, CIKS/p65/c-Jun-dependent ICAM-1 and VCAM-1 expression, and endothelial-monocyte adhesion. Notably, aortas from type 1 diabetic animals (streptozotocin-induced, and autoimmune NOD or Akita) expressed high levels of CIKS, IL-18, and VCAM-1. These results indicate that HG enhances CIKS expression both in vitro and in vivo. Since CIKS mediates HG-induced NF-κB and AP-1-dependent inflammatory signaling and endothelial dysfunction, targeting CIKS may have broader protective effects in vascular diseases, including diabetes mellitus, dyslipidemia, and atherosclerosis.
Abstract 9739: Impact of Statin Use Before the Onset of Acute Myocardial Infarction on Coronary Plaque Morphology of the Culprit Lesion
Authors: Hikita Hiroyuki , Oosaka Yuki , Kawaguchi Naohiko , Nakashima Emiko , Akiyama Daiki , Sugiyama Tomoyo , Kamiishi Tetsuo , Kimura Shigeki , Takahashi Atsushi , Isobe Mitsuaki
Published: April 2024

Statin favorably stabilizes coronary plaque. We evaluated the impact of statin use before the onset of acute ST-elevation myocardial infarction (AMI) on culprit lesion plaque morphology.

Methods:
Patients (n=127, age 63.3 ± 13.1 year old, mean ± SD) with first AMI (within 12 hours after the onset) were divided into either a statin group (n=31) or a nonstatin group (n=96) based on statin use before the onset of AMI. Coronary plaque morphology of the culprit lesion was evaluated using intravascular ultrasound virtual histology (IVUS-VH) with radiofrequency data analysis before coronary intervention. The IVUS-VH identified 4 types of plaque components: fibrous, fibrofatty, dense calcium, and necrotic core. Values of high-sensitivity CRP (hs-CRP) at admission were measured. Dual SPECT using BMIPP and
201
Tl was performed within 2 weeks after the AMI to measure perfusion-metabolism mismatch score, an indicator of viable myocardium, from each total defect score of Tl/BMIPP using 17-segment model and a semiquantitative visual score (0: normal, to 4: no uptake).

Results:
The IVUS-VH showed less percentage of necrotic core area (7.6 ± 6.8% vs 25.5 ± 6.8%, statin vs nonstatin, p<0.001), greater percentage of fibrous area (70.0 ± 14.2% vs 59.0 ± 8.2 %, p<0.001), and greater percentage of fibrofatty area (19.3 ± 12.7 % vs 11.6 ± 9.9 %, p<0.001) of the culprit lesion in the statin group than in the nonstatin group. The values of hs-CRP were lower in the statin group than in the nonstatin group (1.2 ± 0.8 mg/L vs 2.1 ± 2.4 mg/L, p<0.05) The values of mismatch score was higher in the statin group than in the nonstatin group (8.0 ± 2.5 vs 5.3 ± 2.7, p<0.001)

Conclusions:
Statin use before the onset of AMI may have effects on coronary plaque morphology of the AMI culprit lesion with less necrotic core and greater fibrous and fibrofatty component. Reducing necrotic core component of the culprit lesion with statin use before the onset of AMI may be related with lower inflammatory response and greater viable myocardium after AMI.
Abstract 9757: Randomized Trial of Ezetimibe versus Nutraceuticals in Statin-intolerant Patients Treated With Percutaneous Coronary Intervention
Authors: Marazzi Giuseppe , Pelliccia Francesco , Volterrani Maurizio , Righi Daniela , Cacciotti Luca , Campolongo Giuseppe , Sposato Barbara , Grieco Fabrizia , Pasceri Vincenzo , Greco Cesare , Rosano Giuseppe , Gaudio Carlo
Published: April 2024

Treatment with statins has a class IA indication after percutaneous coronary intervention (PCI), but it's often discontinued by patients (pts) due to side effects. Pharmacologic alternatives, including ezetimibe and nutraceuticals (i.e. compounds derived from foods with cholesterol lowering actions), have been shown to be useful after PCI. However, which of these 2 therapeutic approaches is more effective after PCI is still not known. To clarify this point, a prospective, randomized pilot trial has been performed to compare the efficacy and tolerability of ezetimibe vs. a nutraceutical-based protocol in statin-intolerant pts treated with PCI.

Methods
. At time of PCI, 100 pts, with stable angina who had previously experienced statin withdrawn for intolerance, were selected. Pts were randomized to receive for 3 months either ezetimibe (10 mg/day) or a commercially available nutraceutical combined pill (1 capsule/day containing red yeast rice 200 mg, policosanol 10 mg, and berberine 500 mg). Primary outcome included achievement of therapeutic goals by pts, secondary outcomes were plasma lipids levels, tolerability and safety.

Results
. At entry, 50 pts were randomized to ezetimibe (group A) and 50 to nutraceutical combined pill (group B). Baseline clinical features and lipid profiles were similar between groups. During the 3 months trial, 3 patients of group B stopped the pill due to myalgia whereas in the group A 2 patients had gastrointestinal intolerance. At third month evaluation, levels of triglyceride, liver enzymes or creatine kinase were similar between groups. Conversely, while in the group A none of the patients achieved the therapeutic target, 16 patients reached the target in the group B. Also cholesterol level showed a significantly higher reduction in group B compared to group A (in particular, LDL cholesterol decreased from 175 ± 10 to 165 ± 8 mg/dl (-5,8 %) in group A, and from 175 ± 13 to 133 ± 10 mg/dl (-24%) in group B (P=0.001).

Conclusions:
our results strongly suggest that a combination of nutraceuticals with lipid-lowering biological activity can significantly decrease cholesterol levels without causing clinical or metabolic side effects and that it is more effective than ezetimibe 10 mg/day in statin-intolerant patients treated with PCI.
Abstract 9860: Family Caregivers Have Greater Risk of Depression and Cardiovascular Disease than Non-caregivers in Rural Kentucky
Authors: Chung Misook L , Lennie Terry A , Mudd-Martin Gia , Frazier Susan K , Biddle Martha , Casey Baretta , Bailey Alison L , Novak John , Moser Debra K
Published: April 2024

Introduction:
Caregiving is known to be burdensome and to adversely affect physical health. It is not known whether caregiving contributes to increased depression and cardiovascular disease (CVD) risk among adults in rural Kentucky, an area notable for lack of social, economic, and health resources. Thus, the purpose of this study was to examine the association of caregiving with depression and CVD risk factors (i.e., lipids, body mass index (BMI), smoking, and hypertension) in this population.

Method:
Adults in rural Kentucky (n=640; age 50 ± 13.6 years, 75% female) participated in a physical assessment of CVD risk that included BMI, blood lipid profile, and blood pressure. Depression was assessed using the Patient Health Questionnaire-9 (PHQ). The sample was divided into caregivers (13%), family with chronic illness (adults who have a family member with chronic illness but are not caregivers, 18%), and non-caregivers (adults without a chronically ill family member, 69%). Logistic regressions determined the predictive power of caregiving status for depression and CVD risk factors after controlling for age and gender.

Results:
Nearly 20% of participants met criteria for depression; 30% were overweight and 58% obese. Compared to non-caregivers, caregivers were more likely to be depressed (OR = 2.1, 95% CI 1.2 - 3.6, p = .007), a smoker (OR = 2.3, 95% CI 1.2 - 4.4, p = .01), have hypertension (OR = 1.7, 95% CI 1.0 - 2.7, p = .037), lower HDL (OR = 2.0, 95% CI 1.2 - 3.5, p = .007), and higher triglycerides (OR = 1.96, 95% CI 1.2 - 3.2, p = .007). Family members with chronic illness were also more likely to be depressed (OR = 2.6, 95% CI 1.2 - 5.9, p =.021), obese (OR = 1.8, 95% CI 1.6 - 2.8, p = .009), and have hypertension (OR = 1.7, 95% CI 1.0 - 2.6, p = .018) compared with non-caregivers.

Conclusion:
Rural caregivers were at higher risk for depression and CVD. Rural adults with a chronically ill family member were at similar risk for depression but had fewer CVD risk factors than caregivers. Preventive interventions for CVD risk and mental health in rural adults should consider the burden of having a family member with a chronic illness, especially those requiring caregiving.
Abstract 99: A Modified Dispatch Protocol Based on a Layperson’s Description of Breathing Styles of Sudden Cardiac Arrest Victims Is Effective in the Performance of Bystander Cardiopulmonary Resuscitation
Authors: Fukushima Hidetada , Okuchi Kazuo , Seki Tadahiko , Kawai Yasuyuki , Norimoto Kazunobu , Urizono Yasuyuki , Hata Michiaki , Nishio Kenji
Published: April 2024

Introduction: To increase survival from out-of-hospital cardiac arrests (OHCAs), the current guideline for resuscitation emphasizes the role of dispatcher-assisted bystander cardiopulmomary resuscitation (CPR). However, previous studies show that identification of OHCAs by dispatchers is unsatisfactory. Since the callers tend to recognize agonal respiration as a sign of life and perceive as various breathing styles, the current two-question protocol asking the callers whether the unresponsive victim is breathing normally or not is insufficient for the dispatchers to identify OHCA. The aim of this study is to verify a modified protocol for dispatcher-assisted bystander CPR based on the layperson’s description of sudden OHCA breathing styles.

Method: “Not breathing”, “weak breathing”, “unusual breathing or snoring”, and “breathing or not breathing cannot be determined” were identified as the typical layperson descriptions of sudden OHCA breathing styles, based on analysis of dispatcher records from 2007 to 2009 in Nara prefecture, Japan. According to the modified dispatch protocol, dispatchers were to provide CPR instruction when the callers report those key breathing styles. The protocol was implemented in four fire departments which covered an area including 840,000 residents. All data were collected prospectively, using Utstein Style guidelines.

Results: This protocol was carried out for 82 cases of layperson-witnessed OHCA during August to December 2011. Dispatchers instructed CPR for 59 cases of OHCA (71.9%) and callers performed bystander CPR in 41 cases (50.0%). Compared to data from August to December 2010, both the performance of dispatch instruction and dispatcher-assisted bystander CPR significantly improved with the modified dispatch protocol.

Conclusion: A modified dispatch protocol based on the layperson’s description of breathing styles of victims experiencing sudden OHCA significantly improved the performance of bystander CPR.
Abstract 9903: Left Atrial Appendage Contractility Assessed by Speckle Tracking Transesophageal Echocardiography as a Determinant of Thrombus Formation in Patients Receiving Warfarin for Chronic Atrial Fibrillation: beyond CHADS2 and CHA2DS2-VASc Score
Authors: Hirose Takeshi , Kawasaki Masanori , Tanaka Ryuhei , Ono Koji , Watanabe Takatomo , Saeki Maki , Yagasaki Hiroto , Minatoguchi Singo , Miwa Hirotaka , Tokoro Takafumi , Matsuoka Reiko , Abe Sintaro , Goto Yoshiaki , Yoshizane Takashi , Kato Takashi , Kawade Masashi , Warita Shunichiro , Kojima Tai , Iwama Makoto , Noda Toshiyuki , Watanabe Sachiro , Minatoguchi Shinya
Published: April 2024

Background:
Establishment of optimal risk stratification is the best hope for decreasing the burden of atrial fibrillation (AF)-related thromboembolism. Left atrial appendage (LAA) thrombus is a high risk factor of embolism even in AF with warfarin. LAA contractility evaluated by LAA emptying function (EF), strain and radial velocity (RV) of LAA wall motion could contribute to blood stasis and be an important determinant of thrombus in chronic AF, especially in patients with low CHADS2 or CHA2DS2-VASc score.

Methods:
Consecutive 260 chronic AF patients with warfarin were examined and divided into 2 groups according to the presence of thrombus; AF with thrombus (n=43, 69±10) and AF without thrombus (n=217, age 66±11). Each group was divided into subgroup according to CHADS2 or CHA2DS2-VASc score≤2 (low CHADS2 or CHA2DS2-VASc subgroup). LAA EF, peak strain and peak RV of LAA wall were measured using speckle tracking echocardiography. LAA volume, spontaneous echo contrast (SEC) and LAA flow velocity were measured.

Results:
Seventy one % of patients with thrombus and 61% without thrombus met the target INR recommended by Japanese Circulation Society. AF with thrombus had more increased CHADS2 and CHA2DS2-VASc score and reduced LAA EF and strain compared to AF without thrombus (Table). LAA EF and strain were also reduced in low CHADS2 and CHA2DS2-VASc subgroup with thrombus. In multivariate analysis, LAA EF and strain were independent determinants of LAA thrombus. Using 20% of LAA EF as a cutoff, sensitivity and specificity for thrombus were 84% and 90%, using 5 of LAA peak strain, those values were 88% and 76%.

Conclusion:
LAA EF and peak strain were more useful predictors of thrombus in chronic AF than LAA flow velocity, SEC and CHADS2 and CHA2DS2-VASc score. LAA thrombus formation may depend on LAA contractility. Thus, AF patients with reduced LAA contractility should have a strict anticoagulant therapy regardless of CHADS2 or CHA2DS2-VASc score.
Abstract 9904: The Impact of Energy Loss on Cardiac Function in Fontan Circulation
Authors: Honda Takashi , Itatani Keiichi , Kitagawa Atsushi , Ando Hisashi , Nakahata Yayoi , Oka Norihiko , Miyaji Kagami , Ishii Masahiro
Published: April 2024

Background:
There have been several numerical studies discussing the flow energy loss (EL) at Fontan anastomosis that reflects flow efficiencies and which would lead to increase the cardiac workload. However, in-vivo clinical measurements of EL have never been reported. In this study, we measured EL in Fontan patients with simultaneous measurements of pressure and velocity, and revealed its influence to the cardiac functions of the single ventricles.

Methods:
Catheter exams measuring pressure and velocity simultaneously were performed 1 year after the Fontan procedure in 9 patients (mean age 27.4 ± 3.2 months). EL was calculated using the averaged pressure and velocity data of 20 cardiac cycles in the superior and inferior vena cava and the bilateral pulmonary arteries. Systolic functions were evaluated with max dp/dt during the isovolumic systolic phase (Sdpdt), ejection fraction (EF), and cardiac output (CO); whereas diastolic functions were evaluated with max -dp/dt (Ddpdt) and time constant tau in the isovolumic diastolic phase. The ratio of Ddpdt/Sdpdt was examined to detect heart failure with preserved systolic function. Tei index was also examined.

Results:
EL significantly correlated with Sdpdt (r=0.842), but not with EF or CO (r=0.472 and -0.199, respectively), indicating that high EL reflected afterload increase. EL significantly correlated with Ddpdt and tau (r=-0.574 and 0.795, respectively). EL strongly correlated with Ddpdt/Sdpdt and Tei index (r=0.889 and 0.757, respectively), indicating that diastolic function was impaired when EL increased, while systolic function was preserved.

Conclusions:
EL is a novel and sensitive parameter detecting early heart failure with preserved systolic function with increased afterload and impaired diastolic function, and could be an index to decide the indication of medication therapy with vasodilator such as angiotensin-converting enzyme inhibitor for heart failure after Fontan procedure.
Abstract 17989: C-Myc Regulates Substrate Oxidation Patterns During Early Pressure-Overload Hypertrophy
Authors: Ledee Dolena , Smith Lincoln , Kajimoto Masaki , Bruce Margaret , Isern Nancy , Xu Chun , Portman Michael , Olson Aaron
Published: April 2024

Background:
Cardiac hypertrophy alters substrate metabolism towards an increased reliance on glucose utilization. Inactivation of the transcription factor c-Myc (Myc) in the adult myocardium attenuated hypertrophic growth and decreased expression of glycolytic genes in response to aortic constriction. Accordingly, we hypothesize that Myc is an important regulator of substrate utilization for the citric acid cycle during pressure overload hypertrophy.

Methods:
We subjected FVB mice with cardiac specific, inducible Myc inactivation (MycKO) and non-transgenic littermates (Myc-intact) to transverse aortic constriction (n=7/group). After two weeks, function was measured in isolated working hearts along with substrate fractional contributions to the citric acid cycle by using perfusate with
13
C labeled mixed fatty acids, lactate, ketones and unlabeled glucose and insulin.

Results:
Cardiac function was similar between the groups although dP/dT, -dP/dt and developed pressure trended towards improvement in the MycKO mice. MycKO had reduced fractional contribution of fatty acids to the citric acid cycle versus Myc-intact (28%±3 vs 37%±2, p<0.05) along with ketones (19%±1 vs 25%±1, p<0.05). Unlabeled, presumably glucose, contribution increased in MycKO (33%±4 vs 19%±2, p<0.05). While MVO2 was similar between the groups, fatty acid and ketone oxidative flux was decreased in MycKO.

Conclusion:
Myc regulates substrate oxidation preferences during pressure overload cardiac hypertrophy. Further, our data indicates that the change in substrate utilization pattern during hypertrophy is not necessary to maintain cardiac function during this hemodynamic stress.
Abstract 17991: The Cardiolipin-targeting Peptide Bendavia Protects Post-ischemic Myocardium by Preserving Mitochondrial Membrane Fluidity
Authors: Shaikh Saame R , Harris Mitchel , Patel Hetal , Brown David A
Published: April 2024

Bendavia is a mitochondria-targeting peptide currently being tested in the EMBRACE-STEMI trial for reducing injury during acute coronary syndromes. Across pre-clinical models, Bendavia preserves mitochondrial function by targeting the mitochondrial phospholipid cardiolipin, but it is not understood how targeting cardiolipin ultimately leads to cardioprotection. Membrane fluidity, which regulates the assembly of mitochondrial proteins, is directly influenced by cardiolipin levels/content. We recently observed augmented fluidity with Bendavia in cardiolipin-enriched lipid vesicles, but the pathophysiological relevance has not been established. We hypothesized that mitochondrial membrane fluidity would be decreased after cardiac reperfusion, and that targeting cardiolipin with Bendavia protects tissue by sustaining mitochondrial membrane fluidity. Following ex vivo ischemia-reperfusion, rat left ventricular mitochondria were isolated and mitochondrial membrane fluidity was assessed. We utilized two different probes to comprehensively assess mitochondrial membrane fluidity: one that detects acyl side fluidity (DPH polarization; n=6-15 per group), and another that reports on phospholipid headgroup fluidity (MC540 fluorescence (AU); n=3-4 per group). Mitochondrial acyl side chain fluidity decreased after cardiac ischemia-reperfusion (DPH polarization increased 74±16% from control). Phospholipid headgroup fluidity was also decreased following ischemia-reperfusion (mean fluorescence was 535,371 versus 940,139 AU in control). Post-ischemic Bendavia administration improved mitochondrial membrane fluidity in both acyl side chains (mean polarization was increased by only 4% compared to non-ischemic mitochondria) and phospholipid headgroups (mean MC540 fluorescence significantly increased to 804,109 AU). Upcoming studies will determine if improved supercomplex-dependent reparation is a direct consequence of sustaining mitochondrial membrane fluidity. In conclusion, these studies are the first to show clear declines in mitochondrial fluidity during acute coronary syndromes, and highlight the promise of therapies that improve cardiolipin-dependent fluidity.
Abstract 17994: Rad Gtpase Depletion is a Novel Positive Inotrope Without Pathological Signaling
Authors: Manning Janet R , Yin Guo , Magyar Janos , Kaminski Catherine , Feng Han-Zhong , Sievert Gail , Jin J.-P. , Andres Douglas , Satin Jonathan
Published: April 2024

Rationale:
The small GTPase Rad is a negative regulator of voltage-dependent L-type calcium channel (LTCC) current (ICaL); however, the effects of Rad ablation on cardiomyocyte function and calcium homeostasis are unknown. Increased ICa,L may have dual effects , inducing transcriptional regulation in addition to positive inotropism. Alternatively, Rad as a member of the LTCC complex may restrict effects to contractile function only.

Objective:
This study tests the hypothesis that Rad-depletion causes positive inotropic effects without inducing pathological transcriptional signaling.

Methods and Results:
Ventricular myocytes from adult Rad-/- mice were isolated and evaluated for ICa,L and action potentials by patch clamp recordings, as well as calcium transients, and sarcomere shortening. Maximum ICaL is elevated in Rad-/-, decay kinetics are faster, and ICa,L activated at lower voltages thus mimicking effects of beta-adrenergic receptor (β-AR) stimulation. Diastolic and systolic calcium are elevated in Rad-/-, and sarcomere shortening is enhanced, particularly at lower pacing frequencies. Consequentially frequency-dependence of calcium transients is reduced in Rad-/-, and the frequency dependence of relaxation is also significantly blunted. In isolated ex vivo working hearts similar results were obtained, chiefly, contractility (+dP/dt) was elevated at baseline and was less responsive to acute β-AR stimulation. In single cells, at lower infra-physiological frequencies, non-stimulated CaMKII-sensitive calcium release is observed. Remarkably, Rad-/- hearts did not show pathological hypertrophic growth despite elevated levels of diastolic calcium.

Conclusions:
This study demonstrates that the depletion of Rad GTPase parallels β-AR agonism, remarkably without stimulating pathological cardiac hypertrophy. Thus, Rad GTPase is a novel potential therapeutic target for calcium homeostasis-driven positive inotropic support of the heart.
Abstract 17996: Study of the Role of Scn5a in the Occurrence of Arrhythmic Events During Myocardial Infarction and Post-ischemic Remodeling
Authors: Jagu Benoit , Le Tourneau Thierry , Charpentier Flavien , Toumaniantz Gilles
Published: April 2024

The sodium channel Nav1.5, encoded by the Scn5a gene, is responsible for the excitability and the conduction of electrical impulses through the heart. Nav1.5 mutations are involved in rhythmic or structural pathologies. During the acute phase of myocardial infarction (MI), ventricular arrhythmias were associated with an increased risk of mortality. Over time, progressive left ventricular remodeling such as dilation, hypertrophy and fibrosis, will lead to heart failure.

Objectives:
The association of mutations carried by genes encoding for cardiac channels with acquired forms of ventricular arrhythmias and post-ischemic myocardial remodeling, are not well characterized. This project studied the role of Nav1.5 channel alterations in the occurrence of ventricular arrhythmias, structural and contraction abnormalities during the acute phase of MI.

Methods:
The Nav1.5 contribution in this pathological context was evaluated after permanent occlusion of left anterior descending coronary artery performed on mouse invalidated at the heterozygous state for the Scn5a gene (Scn5a+/-; 10-12 w old). After MI validation by echocardiography, they were studied in vivo by echo and electrocardiography and in vitro using molecular investigations during 48 hours post-MI.

Results:
Scn5a+/--MI mice present a higher mortality due to arrhythmic events. In addition, the ECG recorded by telemetry revealed that they present an increased incidence of premature ventricular beats (5.6±2.7 & 33.1±11 PVB/hour respectively for WT & Scn5a+/--MI) without any difference in structural and functional remodelling. However, mRNA expression revealed that Scn5a+/--MI mice have an increased up-regulation of pro-inflammatory factors IL-6 (3.7±0.9 & 17.4±9.3 Relative Quantity respectively) and IL-1β mRNA (1,8±0.3 & 4.6±0.8 RQ respectively) and downregulation of Cx43 mRNA (0.61±0.08 & 0.39±0.03 RQ respectively) without interstitial fibrosis induction.

Conclusions:
These observations, 48 hours post-MI, suggest that Scn5a+/- mice present factors for the establishment of a more severe post-ischemic heart failure. In addition, preliminary results obtained on small series of animals revealed that Scn5a+/- mice seem to have a more pronounced LV remodelling at 4 weeks post-MI.
Abstract 18003: 9p21 is Associated With Risk of First but Not Recurrent Major Adverse Cardiovascular Events
Authors: Patel Riyaz S , Asselbergs Folkert W , Quyyumi Arshed A , Hemingway Harry , Hingorani Aroon , Holmes Michael V
Published: April 2024

Background:
The chromosome 9p21 locus is a recognized risk factor for coronary heart disease (CHD). Emerging data suggest that it may not confer additional risk in patients with established CHD. We sought to examine the association of 9p21 with first and recurrent major adverse cardiovascular events (MACE) through systematic review and meta-analysis.

Methods:
We searched PubMed and EMBASE from inception to May 2013. All prospective studies reporting association for 9p21 and MACE (comprising any combination of death, fatal/nonfatal MI, revascularisation) were included. We supplemented identified studies with two unpublished cohorts. Data on clinical setting (healthy/established CHD), outcomes assessed and per-allele effect size and confidence limits were extracted. In 6 studies reporting data separately by 9p21 genotype, we estimated the per-allele effect using meta-regression. We performed a meta-analysis, stratified by clinical setting, and compared estimates using the Altman & Bland test for interaction.

Results:
We identified 32 cohorts of which 3 were excluded as reported estimates could not be incorporated into meta-analysis. In 15 studies, of 161,043 individuals predominantly free of CHD and with 14,827 events, 9p21 associated with a pooled HR for a first event of 1.19 (95% CI: 1.17, 1.22). In contrast, in 14 studies of 25,059 patients with established CHD, reporting 4,628 events, the pooled HR of 9p21 for recurrent MACE was 1.02 (95% CI: 0.98, 1.06). There was strong evidence of heterogeneity between the estimates for first and recurrent MACE (P=1.1x10-11 for heterogeneity).

Conclusions:
In contrast to association with first MACE, 9p21 may not associate with recurrent MACE in patients with established CHD. This may reflect mechanistic differences in disease onset versus progression or attenuation of effect by CHD therapies. With implications for genetic risk prediction, further studies are needed to precisely define the role of 9p21 in those with CHD.
Abstract 18014: Image-Based Patient-Specific Simulations of Ventricular Electrophysiology for Sudden Arrhythmic Death Risk Stratification
Authors: Vadakkumpadan Fijoy , Arevalo Hermenegild , Jebb Alexander , Wu Katherine C , Trayanova Natalia
Published: April 2024

Low left-ventricular ejection fraction (LVEF), the main criterion used in current clinical practice to stratify sudden arrhythmic death (SAD) risk, and select patients for prophylactic implantable cardioverter defibrillator (ICD) treatment, has very low sensitivity and specificity. Arrhythmia inducibility in clinical electrophysiological study (EPS) can improve SAD risk prediction, but it is invasive and expensive. We seek to demonstrate that image-based patient-specific simulations of ventricular electrophysiology can be used as a non-invasive and economical surrogate for clinical EPS in predicting SAD risk. Data from 20 patients with myocardial infarction and low LVEF, who were scanned with late gadolinium enhanced cardiac MRI prior to ICD implantation, and followed for appropriate ICD firing and SAD, were used. Nine patients had events and eleven did not. For each patient, a multiscale, biophysically-accurate ventricular model, including inexcitable scar, electrically remodeled gray zone, and estimated fiber orientations, was built from the image data. A programmed electrical stimulation (PES) protocol with 2 ventricular extrastimuli, similar to that used clinically, was performed in each model from 17 LV endocardial sites corresponding to the 17 AHA regions. An inducibility index was calculated for each patient as the proportion of the PES sites from which sustained ventricular arrhythmia was induced. The mean inducibility index was 0.21±0.14 for patients who had an event vs. 0.09±0.14 for those who did not (p<0.05). The figure shows geometries and simulated activation maps of a patient without event (top row) and with event (bottom row). All patients with events had inducibility stimulated from at least 1 site (range: 1-8). In conclusion, we have developed a new index computed from noninvasive simulations of ventricular electrophysiology, that may be able to stratify SAD risk and guide prophylactic treatment delivery.
Abstract 18019: Race and Sex Sensitive Stroke Risk Prediction: Analysis of Pooled Data From Atherosclerosis Risk in Communities (ARIC) and Cardiovascular Health Study (CHS) Cohorts
Authors: Pandey Dilip K , Zhao Weihan , Bhaumik Dulal K , Gorelick Philip B
Published: April 2024

Context:
A risk assessment tool predicting increased risk of first stroke helps to identify at-risk individuals and aid in development of intervention strategies leading to the primary prevention of stroke. Most relied-upon Framingham Heart Study (FHS) stroke risk profile (FRS) does not include race due to lack of information on race other than white in FHS.

Objective:
To develop a race and sex sensitive risk score for incident stroke.

Methods:
Risk prediction functions were estimated using pooled data from the ARIC and CHS studies on 16,379 participants (55% women, 23% black) with 1,363 (8.3%) incident stroke during 263,295 person-years with median follow-up 18.3 years. Study sample included individual ages 45-84 years and free of stroke and cancer at the initial examination. Study sample did not include stroke events or individuals lost due to other events or follow-up during the first year as well as individuals with missing data on factors of interest. Cox proportional hazards regression analysis was performed after confirming the proportionality of hazards. Akaike (AIC) and Bayesian information criterion (BIC) was used to develop the best fitting model.

Results:
The risk equation included age, sex, race (non-black/black), left ventricular hypertrophy, peripheral arterial disease, current smoking, prior myocardial infarction, atrial fibrillation (AF), waist to hip ratio, systolic blood pressure (SBP), and diastolic blood pressure, use of antihypertensive therapy (HTNMED), fasting blood sugar and serum creatinine. The risk equation also included interactions between age x race, age x sex, race x AF, and SBP x HTNMED. All predictors included were significantly associated at p <0.05 except for race x AF (p = 0.078). The risk equation demonstrated good discrimination (Harrell’s C = 0.7877) with receiver operator (ROC) curve statistics for 10-year stroke risk of 0.7521 for non-black and 0.7012 for black. The ROC curve statistics for 10-year stroke risk estimated from the FRS were 0.7099 for non-black and 0.6552 for black.

Conclusion:
This improved stroke risk predictions derived from a large population based data provide race and sex sensitive risk prediction of first stroke based on predictors readily available during routine clinical examination.