bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 19: Cardiopulmonary Resuscitation by Bystanders with Chest Compressions Only for Children with Witnessed Out-of-Hospital Cardiac Arrest
Authors: Shimizu Naoki , Ohta Kunio , Nitta Masahiko , Yonemoto Naohiro , Nonogi Hiroshi , Nagao Ken , Kimura Takeshi , Japanese Paediatric Resuscitation Study (PReSS) Group  , JCS-ReSS group
Published: April 2024

Background: Conventional cardiopulmonary resuscitation (CPR) is a barrier to bystanders including parents doing CPR for children. Particularly mouth-to-mouth ventilation has been considered to be difficult to teach and perform. Several clinical studies have shown the efficacy of bystander CPR by chest compression only (CC-only) for adults, but not yet stated enough for children.

Methods: In a nationwide out-of-hospital cardiac arrest (OHCA) registration from 2005 to 2010, we enrolled 11,417 children aged less than 18 years old. Data collected include age, etiology, ECG wave form, type of CPR, and neurological outcome. Favorable outcome was defined as cerebral performance category 1 or 2.

Results: 3,486 (31%) children with OHCA were described as cardiac etiology, and 7,931 (69%) as non-cardiac. VF/pulseless VT (VF/pVT) in 546 (5%) cases, PEA in 1,668 (15%), and asystole in 8,168 (71%). 3,041 (27%) cases received conventional CPR, 2,421 (21%) received CC-only CPR, and 5,507 (48%) were given no CPR. Within 2,808 (25%) children with witnessed citizen bystanders, 706 (25% of 2,808) received conventional CPR and 577 (21% of 2,808) received CC-only CPR, but outcome was not available in 69 cases. Any CPR comparing with no CPR (8.5% [463/5,462] vs 3.1% [168/5,507]; OR 2.78, 2.32-3.32), or conventional CPR comparing with CC-only (11% [329/3,041] vs 5.5% [134/2,421]; OR 1.95, 1.59-2.40) showed higher favorable outcomes. However, analysis in children with witnessed citizen bystanders revealed no difference on favorable outcome between conventional CPR and CC-only CPR (9.0% [60/668] vs 7.5% [41/546]; OR 1.22, 0.80-1.83). In each waveform group (VF/pVT; 32% [38/118] vs 29% [25/86]; OR 1.11, 0.62-1.97, PEA 7.1% [11/156] vs 6.3% [9/142]; OR 1.11, 0.45-2.76, Asystole 3.1% [11/353] vs 2.2% [7/318]; OR 1.42, 0.54-3.69), even excluding infants (11% [56/514] vs 8.0% [35/438]; OR 1.36, 0.88-2.11), indicated same trends.

Conclusion: CC-only CPR by witnessed citizen is equally effective for children who have witnessed OHCA, comparing with conventional CPR. Enhancement of citizen bystander CPR including children with uniform BLS algorithm is reasonable, and need to be enriched further to diminish paediatric OHCA events without bystander CPR.
Abstract 19052: Preoperative Non-invasive RVSP Correlates Poorly with Invasively Measured Pulmonary Artery Systolic Pressure During General Anesthesia
Authors: Jain Sonia , Subramanian Arun
Published: April 2024

Introduction:
Pulmonary hypertension (PH) is an independent marker of surgical morbidity. Right ventricular systolic pressure (RVSP) measured by transthoracic echocardiography (TTE), correlates poorly with pulmonary artery systolic pressure (PASP) measured by right heart catheterization, especially in PH. The correlation between TTE derived RVSP and intraoperative PASP, while under general anesthesia, is not known. In this study, the association between preoperative RVSP and intraoperative PASP was tested.

Methods:
All consenting adult surgical patients requiring intraoperative pulmonary pressure monitoring in a 2 year period were retrospectively identified. Patients who had TTE estimated RVSP ≥ 40 mmHg, measured within a week prior to the index surgery, were included. RVSP was calculated from tricuspid regurgitant velocity using the modified Bernoulli equation. For intraoperative PASP, the median of the first 10 minutes after PAC placement was used. CVP, arterial systolic pressure, minimum alveolar concentration of anesthetic (MAC) and basic demographic data were also collected. Agreement between RVSP and PASP was tested using the concordance correlation coefficient. Multivariate linear regression and Bland-Altman plot were used to further refine the analysis.

Results:
129 patients met inclusion criteria. Median age (IQR) was 73 (62 - 79) years; TTE was performed a median (IQR) of 2 (1 - 3) days prior to surgery; mean (SD) RVSP was 56.1 (±12.4) mmHg and mean (SD) PASP was 42.1 (±14.9) mmHg. Concordance correlation coefficient between RVSP and PASP was only 0.13 (95% CI 0.02 - 0.24). On multivariate linear regression, PASP was significantly associated with RVSP and CVP (p < 0.01), but not anesthetic MAC, age or proximity of measurements. Bland-Altman bias was -13.9 mmHg; 95% limits of agreement were -48.0 to +20.1 mmHg.

Conclusion:
Preoperative RVSP measured by TTE correlates poorly with intraoperative PASP measured by PAC during general anesthesia.
Abstract 19134: Higher Red Blood Cell Distribution Width Predicts Cardiovascular Events in Patients with Heart Failure with Normal Left Ventricular Ejection Fraction
Authors: Akiyama Eiichi , Sugiyama Seigo , Konishi Masaski , Nozaki Toshimitsu , Ohba Keisuke , Matsubara Junichi , Sumida Hitoshi , Kaikita Koichi , Kimura Kazuo , Umemura Satoshi , Ogawa Hisao
Published: April 2024

Background
Red blood cell distribution width (RDW) is a quantitative measure of the variability in size of the circulating erythrocytes, and is associated with increased risk of adverse cardiovascular (CV) outcomes in patients with heart failure (HF) with reduced left ventricular ejection fraction (LVEF). We investigated whether the RDW levels could predict future CV events in patients with HF with normal LVEF (HFNEF).

Methods
We measured plasma levels of B-type natriuretic peptide (BNP) and RDW sampled from peripheral vein following an overnight fast in 319 patients with symptomatic HF (New York Heart Association (NYHA)-II: n=244, -III, IV; n=75, age 71±10, LVEF 63±6%, BNP 121 [33-302] pg/ml]). HFNEF patients were followed until occurring CV events (CV death, non-fatal myocardial infarction and ischemic stroke, unstable angina pectoris, hospitalization for HF, or coronary revascularization).

Results
RDW levels were higher in patients with moderate to severe symptoms (NYHA III or IV) compared to mild symptoms (NYHA II) (14.1±1.4 vs. 13.4±1.0%, P<0.001). RDW positively correlated with BNP (r=0.42, P<0.001), and C-reactive protein (r=0.28, P<0.001), whereas RDW inversely correlated with hemoglobin levels (r=-0.30, P<0.001), LVEF (r=-0.22, P<0.001), and estimated glomerular filtration rate (r=-0.21, P<0.001). During a mean follow-up of 20 months, 59 patients developed CV events. RDW levels was significantly higher in patients with CV events than those without events (13.9±1.5 vs. 13.5±1.1%, P=0.03). Kaplan-Meier analysis demonstrated a significantly higher probability of CV events in the higher RDW group (n=34) than in the lower RDW group (n=285) by the cut-off value as 15.0 (log rank test P<0.001). Multivariate Cox hazard analysis identified higher RDW [hazard ratio (HR) 2.00, 95% confidence interval (CI) 1.04-3.88, P=0.04], higher NYHA class (NYHA III or IV, HR 2.69, 95% CI 1.53-4.75, P=0.001), and higher BNP levels (a cut-off value 100pg/ml, HR 2.25, 95% CI 1.16-4.37, P=0.02), but not hemoglobin levels, as independent predictors of the future CV events.

Conclusions
Levels of RDW correlated with HF severity, LVEF, anemia, inflammation, and renal function, and higher RDW predicted the future CV events in patients with HFNEF.
Abstract 19155: The Impact of Expeditious Management of Perioperative Myocardial Ischemia in Patients Undergoing Isolated Coronary Artery Bypass Surgery
Authors: Davierwala Piroze , Verevkin Alexander , Leontyev Sergey , Misfeld Martin , Borger Michael A , Mohr Friedrich W
Published: April 2024

Objective: To analyze the effect of immediate treatment of perioperative myocardial ischemia due to early graft failure in patients undergoing coronary artery bypass surgery (CABG).

Patients and methods: Between January 2004 and December 2010, 7489 patients underwent isolated CABG at our institution. All patients (n=427, 5.7%) who showed evidence of perioperative myocardial ischemia (PMI) underwent emergent coronary angiography. PMI was characterized by an isoenzyme ratio of creatinine phosphokinase (CK/CK-MB) > 10% and/or new ST-segment changes and/or recurrent episodes of ventricular tachycardia or fibrillation and/or hemodynamic deterioration with new regional wall motion abnormalities on echocardiography. One thousand and thirteen grafts and 1131 distal anastomoses were examined angiographically.

Results: One hundred and seventy-six patients had a normal postoperative coronary angiography. Two hundred and fifty-one patients had stenoses or occlusions of 372 grafts. Revision CABG (group A) or percutaneous coronary intervention (PCI) (group B) was performed in 130 (51.8%) and 31 (12.4%) patients with graft stenosis or occlusion, respectively. Conservative therapy was implemented in 92 (36.6%) patients (group C). In-hospital mortality was 8.4% and 2.9% in patients with and without PMI (p < 0.001). In the former group, in-hospital mortality was 10.4% and 5.7% in patients with and without graft failure, respectively (p=0.087). There was no difference in early and long-term survival between the 3 treatment groups for graft failure (p=0.8). On the other hand, 1- and 5-year survival in patients with no PMI (93.3±0.03% and 83.6±0.05%, respectively) was significantly better than those with PMI (92.3±0.1% and 82.4±0.2%, respectively) [p<0.001 log rank]. When in-hospital mortality was excluded, there was no difference (p=0.1) in long-term survival between patients with and without perioperative myocardial ischemia.

Conclusions: Perioperative ischemia is associated with increased in-hospital mortality in patients undergoing isolated coronary bypass surgery. Expeditious treatment of bypass graft stenosis or occlusion results in similar long-term survival to non-ischemic patients in hospital survivors.
Abstract 19196: Resveratrol Prevents the Oxidative Stress and Diastolic Dysfunction in Iron-overload Cardiomyopathy
Authors: Das Subhash K , Patel Vaibhav B , Kazemi-Bajestani Seyyed M.R. , Zhabyeyev Pavel , Dyck Jason R , Oudit Gavin Y
Published: April 2024

Introduction:
Iron-overload cardiomyopathy results in heart failure with high morbidity and mortality. Iron-overload results in iron-induced oxidative stress and organ dysfunction and is associated with genetic and acquired iron-overload conditions. Resveratrol is a natural polyphenol with a broad range therapeutic potential.

Hypothesis:
We hypothesized that resveratrol will reduce iron-induced oxidative stress and prevent iron-overload cardiomyopathy.

Methods and Results:
Iron-overload cardiomyopathy was induced by treating 10 week old male C57Bl6 mice sub-acutely with iron-dextran at 5 mg/25g body weight i.p, 5 days/week for 4 weeks. The antioxidant and metabolic modulator, resveratrol was given at 190 mg/kg/day. Quantification of tissue iron showed significant deposition in the heart (350±27 vs 5304±773 µg/mg tissue; n=10, p<0.01) which was confirmed by Prussian blue staining. Hemodynamic (+dP/dt/-dP/dt
max
ratio=1.0 vs 1.7; n=6) and echocardiographic (E/A ratio: 1.46±0.043 vs 1.27±0.06, n=6, p<0.05; E’/A’ ratio: 0.77±0.04 vs 1.20±0.05, n=7, p<0.01) analysis showed diastolic dysfunction with preserved systolic function in iron-overload hearts in the absence of increased myocardial fibrosis. Resveratrol treatment prevented the development of diastolic dysfunction (E/A ratio:1.27±0.06 vs 1.67±0.13 and E’/A’:1.2±0.05 vs 0.80±0.02; n=7, p< 0.01; hemodynamic: +dP/dt/-dP/dt ratio: 1.6 vs 1.1 n=6, p<0.01) without altering the degree of iron-overload (5200±743 µg/mg tissue ; n=10). Increased expression of ANF (65%), BNP (103%) and β-MHC (44%) showed a complete normalization with resveratrol treatment. Expression of oxidative stress-related genes, thioredoxin (91%), catalase (140%), glutathione peroxidase (548%) and superoxide dismutase (87%) were increased in iron-overload mice treated with resveratrol with a complete normalization of reduced glutathione levels in the heart (GSH: 50 vs 250ng/mg tissue).

Conclusions:
Iron-overload resulted in oxidative stress mediated selective diastolic dysfunction with preserved systolic function. Treatment with resveratrol can prevent oxidative stress and myocardial injury and protect the heart from the iron-overload induced diastolic dysfunction.
Abstract 19199: Cardiomyocyte Enriched MicroRNA, Mir-378, Regulates Hypertrophy Agonists Stimulated Growth of Cardiac Myocytes
Authors: Nagalingam Raghu S , Solaro R J , Gupta Mahesh P , Sundaresan Nagalingam R , Gupta Madhu
Published: April 2024

MicroRNAs are small non-coding RNAs that have emerged as important negative regulators of gene expression. We recently described miR-378 as a cardiomyocyte enriched miRNA that targets IGF1/IGF1R signaling and regulates post-natal cardiac remodeling (
JBC 287(16):12913-26, 2012
). In this study we tested the hypothesis that miR-378 regulates cardiomyocyte growth induced by hypertrophy stimuli. To test miR-378 involvement in cardiac hypertrophy, pressure overload was induced in adult mice by transverse aortic constriction (TAC) for 2 wks or 8 wks. TAC produced about 40% increase in HW / tibia length ratio with no overt cardiac dysfunction at 2 wks (hypertrophy, H group) and 30% reduction in %FS at 8 wks (heart failure, HF group). Expression of miR-378 was reduced by about 50% in H group but it was induced by 1.2-fold in HF group. Deficiency of miR-378 (30% to 60%) was also noted when neonatal rat ventricular cardiomyocytes (NRVM) were exposed to hypertrophy agonists, phenylephrine (PE, 20uM), AngII (100 nM) or isoproterenol (10 uM) for 48 h. Inhibition of miR-378 in NRVM by 378-antimiR, resulted in enhanced PE stimulated cardiomyocyte growth as reflected by 25% increase in cardiomyocyte size by WGA staining. We also noted significatly more induction of ANF in response to PE treatment in 378-antimiR transfected NRVM as compared to scramble control. Conversely, over-expression of miR-378 by 378-mimic in NRVM led to significant inhibition of PE induced
[3]
Leu incorporation and ANF induction. It also counteracted PE-stimulated activation of Ras and downstream signaling cascade such as pERK1/2, p70S6K and pAKT. One of the well accepted markers of pathological remodeling is nuclear translocation of NFATC which activates hypertrophy gene program in response to hypertrophy stimulus. By confocal imaging we found 378-mimic totally obliterated nuclear occupancy of NFATC 48 h after PE treatment. Data indicate that deficiency of miR-378 contributes to the development of cardiac hypertrophy, and by inhibiting Ras-signaling, miR-378 acts as an anti-hypertrophy microRNA. Our findings implicate that over-expression of miR-378 will counteract pathological remodeling and protect the heart from maladaptive hypertrophy and heart failure.
Abstract 19310: High Frequency QRS Analysis has Incremental Diagnostic Accuracy Over ST-Segment Analysis Alone for Ischemia Identification in Patients Referred for Exercise Myocardial Perfusion Imaging
Authors: Perez Margarita , Izarnotegui Valerie , Watson Denny , Sobczak Michael , Beller George , Bourque Jamieson
Published: April 2024

Introduction:
Myocardial perfusion imaging (MPI) to identify ischemia is expensive, but existing electrocardiographic techniques have poor sensitivity. A novel method of high-frequency QRS analysis (HF-QRS) may improve ischemia detection. We sought to compare HF-QRS to standard ST-segment analysis for the identification of any and significant (≥10%) left ventricular (LV) ischemia by exercise SPECT MPI.

Methods:
We analyzed 292 consecutive patients. HF-QRS was determined within a bandwidth of 150 -250 Hz. A 50% relative reduction and ≥1 µV drop in the HF-QRS signal in ≥3 leads and ≥1mm ST-depression were the criteria for positivity for HF-QRS and ST-analysis, respectively. Quantitative, gated-SPECT MPI was performed according to standard protocols. Sensitivities and specificities and incremental diagnostic accuracy were assessed using chi-square and logistic regression analyses.

Results:
The mean cohort age was 59.6 years and 64.7 were male. Twenty nine percent had known coronary artery disease. LV ischemia was present in 54 patients (18.4%) and significant (≥10%) LV ischemia in 17 (5.8%). ST-analysis and HF-QRS analyses were positive in 42 (14.4%) and 70 (23.9%) respectively. As shown in the figure, ST-analysis had poor sensitivity for any ischemia that improved but remained low for ≥10% LV ischemia. HF-QRS had substantially higher sensitivities for both any and ≥10% LV ischemia. The 84.9% specificity of HF-QRS analysis for any ischemia was similar to the 86.6% specificity of ST-analysis. ST depression failed to add incremental diagnostic information to clinical risk factors (p=0.519), while HF-QRS increased the model Χ2 from 39.3 to 54.2 (p<0.001).

Conclusions:
High-frequency QRS analysis substantially improves the detection of any and significant ischemia over ST-segment analysis alone in patients undergoing exercise stress. This novel method has the potential to decrease the high rate of MPI for CAD risk stratification.
Abstract 19364: Coronary Plaque Characteristics by Age and Sex in Healthy Individuals with a Family History of Early-Onset Coronary Artery Disease
Authors: Kral Brian G , Becker Diane M , Vaidya Dhananjay , Yanek Lisa R , Qayyum Rehan , Moy Taryn F , Fishman Elliot K , Becker Lewis C
Published: April 2024

Background:
Although calcified coronary plaque (CCP) increases with age and is more prevalent in males, the extent to which noncalcified plaque (NCP) is present across the age range of both sexes is unknown. This has important implications for primary prevention guidelines, particularly in high risk populations, since NCP is a putative immediate precursor for coronary artery disease (CAD) events. We thus examined total coronary plaque (TCP), CCP, and NCP distributions in healthy male and female first degree relatives of persons with early-onset CAD.

Methods:
Participants in GeneSTAR (N=561), mean age 51.5 ± 10.8 years, range 30 to 75 years, 58% female, were screened for coronary plaque using 256 multidetector dual-source CT angiography. Segmental plaque volumes (mm3) were quantified using an automated well-validated proprietary method and summed for CCP and NCP. TCP was calculated from CCP+NCP.

Results:
Males had a higher prevalence of any coronary plaque compared to females, (58.1% vs 36.7% respectively, p<0.0001); plaque prevalence increased significantly with age (Table). However, females more often had only NCP than males, (17.6% vs 8.9%, p= 0.11). CCP and NCP volumes both increased with age in both sexes, but NCP accounted for more than half of TPV in both sexes at all ages; NCP represented more than 80% of TPV in subjects <55 years of age.

Conclusion:
The majority of TPV was noncalcified plaque in this healthy high risk population, particularly in females and in males <55 years old. Thus, conditioning aggressive primary prevention on traditional coronary calcium scoring algorithms, may obviate appropriate risk reduction interventions in young persons with a family history of early onset-CAD. Table: Sex-specific noncalcified and calcified coronary plaque volumes by age group (median [IQR])
Abstract 19374: Predictors of Cardiovascular Events in Patients after Coarctation Repair
Authors: Luijendijk Paul , Lu Ling , Vriend Joris , Vliegen Hubert , Groenink Maarten , Groenink Maarten , Bouma Berto , Mulder Barbara
Published: April 2024

Background:
Long-term outcome after coarctation repair (CoA) is characterized by a significant cardiovascular morbidity and mortality Little is known on the predictive value of clinical parameters on cardiovascular events in CoA. The aim of this study is to determine the predictive value of clinical parameters on cardiovascular events.

Methods:
160 adult CoA patients were identified in 2001 and followed for the occurrence of cardiovascular events until 2012. Echocardiography, ambulatory blood pressure monitoring, CMR imaging, and imaging of the carotid arteries (CIMT) were performed at baseline. The composite endpoint included: myocardial infarction, ischemic or hemorraghic cerebrovascular events, heart failure, aortic aneurysm formation requiring an intervention, and sudden cardiac death.

Results:
160 adult CoA patients were included (mean age of 31.7 ±11.5 years and mean age at repair 4.3 ±6.6 years, 64% male) and followed with a mean follow-up of 10.10 ± 0.71 years; 18 (11%) patients suffered from an event during follow-up. Five patients (3%) had myocardial infarction, 4 (3%) an ischemic cerebrovascular accident, 7 (4%) an aortic aneurysm which needed surgical intervention, and 2 patients (1%) died suddenly. Univariate Cox regression analysis revealed that older age (ß = 1.08, P < 0.001), elevated total cholesterol levels (β = 4.4; p = 0.03), elevated LDL cholesterol levels (β = 3.1, P = 0.09) and the carotid intima media thickness (β = 309.6; p = 0.007) were associated with an event during follow-up. Multivariate analysis demonstrated that patients with older age (β = 9.8, P = 0.02), increased total cholesterol levels (β = 1.24, P = 0.09) and an increased CIMT (β = 12.5, P = < 0.001) were specifically at risk for a cardiovascular event during follow-up. Cumulative event-free survival was significantly lower in patients with a CIMT above 0.61 mm (median) (P = 0.09, HR: 2.23) (Figure 1)

Conclusions:
During 10 year follow up almost 11% of CoA patients suffered from a cardiovascular event. Older age, elevated cholesterol levels and an increased CIMT were the main determinants. Overall event-free survival is significantly lower in patients with an increased CIMT. Intervention with statin therapy might improve the prognosis of these young patients in the future.
Abstract 19379: Failure of Regenerative Cell-Based Therapy to Stimulate Coronary Collateral Growth in a Rat Model of Metabolic Syndrome
Authors: Logan Suzanna , Chilian William M , Ohanyan Vahagn A , Stevanov Kelly , Enrick Molly , Kolz Christopher L , Yin Liya
Published: April 2024

Nearly 30-40% of patients with coronary disease show little or no coronary collateral growth and have a poorer prognosis than those with well-developed collaterals. Stem cell therapies hold promise for stimulating vascular growth in the heart, but most results to date have been modest. Perhaps stem cell survival and differentiation are compromised by the oxidative environment occurring in cardiovascular disease. To test this, we determined if cell-based regenerative therapies stimulate coronary collateral growth in a rat model characterized by oxidative stress and poor coronary collateralization. Previously we found that induced vascular progenitor cells (iVPCs) were the best cell type (compared to MSCs and iPS cells) to stimulate coronary collateral growth in lean (LN) rats (10-day repetitive ischemia [RI] protocol). Using the RI protocol, iVPCs were implanted intramuscularly in the heart of Zucker Obese Fatty (ZOF) rats. Coronary collateral flow was significantly increased by iVPCs in LN but not in ZOF (Figure 1), suggesting that under oxidative stress, iVPCs fail to induce coronary collateral growth. To understand why iVPCs did not stimulate collateral growth in ZOF rats, we mimicked conditions of oxidative stress and mitochondrial DNA damage in ZOF rats (previously observed in our lab) by treating the cells with H
2
O
2
(100 µM or 800 µM) for 2 hrs followed by 100 µM 4-Nitroquinoline 1-oxide for 1 hr. These stressors decreased viability of iVPCs by 19.8% and 62.7% (high and low H
2
O
2
; p<0.05; MTT assay) and decreased the expression of stemness lineage markers for SSEA1, CD133, and c-kit by 79%, 84% and 67%, respectively (real-time PCR). These data indicate that oxidative stress in ZOF rats compromises cell survival and stemness of the implanted iVPCs, limiting their regenerative potential. Our results suggest that consideration of adjunctive therapies to improve cell survival and regenerative capacity is important in cell-based therapies for vascular disease.
Abstract 19482: Integrated Non-Invasive Imaging Approach for Assessment of Tissue Perfusion, Oxygenation, and Collateralization in a Porcine Model of Peripheral Artery Disease
Authors: Stacy Mitchel R , Sampath Smita , Yu Da Yu , Maxfield Mark W , Jozwik Bartosz P , Hawley Christi L , Dione Donald P , Kolodziej Andrew R , Lin Ben A , Zhuang Zhen W , Pal Prasanta , Sinusas Albert J
Published: April 2024

Objectives:
Currently, there is no standard quantitative imaging approach to evaluate peripheral artery disease (PAD).In this study, we use hybrid SPECT/CT and MR imaging to relate post-occlusion collateral formation to serial
in vivo
changes in lower extremity perfusion and tissue oxygenation before and during vasodilation.

Methods:
Serial hybrid 64-slice CT/SPECT imaging and BOLD MRI were performed in pigs (n=8) at baseline, immediately post unilateral femoral artery occlusion, and 1 and 4 weeks post occlusion. Contrast X-ray CT angiography was performed to define the occlusion site and to visualize collateral vessels. Non-contrast CT images were used to identify individual muscle groups in the ischemic (I) and non-ischemic (NI) hind limb for quantification of changes in relative regional muscle perfusion with
201
Tl SPECT. At 4 weeks post occlusion, muscle
201
Tl activity was measured postmortem by gamma well counting. MR images were acquired on a 3T magnet and T2* maps were generated for multiple transverse images. BOLD images used to quantify tissue oxygenation were acquired for 5 minutes at rest and for 10 minutes during vasodilation by IV administration of nitroglycerin (5 mg/kg/min NTG).

Results:
SPECT/CT imaging showed a significant decrease in regional
201
Tl activity (I/NI) (Fig. 1A) in ischemic calf muscle groups (Fig. 1B), which normalized over time. Relative
201
Tl activity at 4 weeks (0.91±.0.06) matched gamma well counting (0.99±0.08, p=ns). These changes were not observed in other muscle groups. The T2* signal intensity in the ischemic leg decreased acutely post occlusion in response to NTG, probably reflecting diminished vascular reserve, although this response normalized at 4 weeks in association with collateral vessel formation.

Conclusions:
Physiological changes in tissue perfusion and oxygenation following peripheral ischemia were tracked non-invasively using multimodality imaging, and can be attributed to collateral formation.
Abstract 19559: Risk of Atrial Fibrillation is Increased in Patients with Autoimmune Vasculitis: A Population-Based Cohort Study
Authors: Melduni Rowlens M , Nazmul Mohammed N , Amin Shreyasee , Gersh Bernard J , Bailey Kent R , Cha Stephen S , Cooper Leslie T , Seward James B , Lee Hon-Chi
Published: April 2024

Introduction
Current evidence suggests that abnormal ventriculo-vascular coupling may contribute to the development of atrial fibrillation (AF) by increasing ventricular filling pressures and consequently, left atrial pressure. Recent investigations have also suggested that inflammation might have a role in the pathophysiology of AF. We hypothesize that autoimmune vasculitis plays a significant role in the pathogenetic mechanism of AF.

Methods
In this longitudinal cohort study, residents of Olmsted County, MN with first- time diagnosed AF during 1980-2000 and a reference age- and sex-matched control group from the same underlying population and time period were identified and followed until death, or 2000. The relationship between autoimmune vasculitis and first documented AF was analyzed.

Results
Of a total of 8766 patients (mean age 61.1+14.9 years; 56% women), 691 (7.9%) were diagnosed with autoimmune vasculitis during the 20 year period. The prevalence of autoimmune vasculitis in the AF group was 9.9% and 5.9% in the control group; p <0.001, respectively. After adjusting for CAD and LV dysfunction, the odds of autoimmune vasculitis in AF was 1.7 times higher than in controls (OR 1.69, 95%; CI 1.42 - 2.01, p < 0.0001). AF patients with autoimmune vasculitis had a worse survival compared to controls; p=.0114 (log-rank test).

Conclusion
Autoimmune vasculitis strongly increases the risk of atrial fibrillation and portends shorter survival in the AF population. These observations may represent one mechanism linking increased arterial stiffness and inflammation in the pathogenesis and prognosis of AF as an age-related disorder.
Abstract 19629: Expression and Role of TRPC Channels in Cardiomyocytes Derived from Human Induced Pluripotent Stem Cells
Authors: Wen Hairuo , Allen Charelle , Fefelova Nadezhda , Xie Lai-Hua
Published: April 2024

Store-operated Ca
2+
entry (SOCE) is a mechanism for increasing cytosolic Ca
2+
(Ca
i
2+
) load after the SR/ER Ca
2+
depletion in many cell types. Our previous study has implicated SOCE, which is at least partially mediated by transient receptor potential canonical (TRPC) channels, exists in adult mouse ventricular myocytes, and contributes to the generation of spontaneous SR Ca
2+
release and triggered arrhythmias. However, it is unclear if this mechanism also exists in human cardiac myocytes. In the present study, we investigate the expression and role of TRPC channels in cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) (purchased from Cellular Dynamics). Abundant distributions of TRPC3 and 6 channels were detected in the plasma membrane of hiPSC-CMs using immunocytochemical staining. Ca
i
2+
was imaged in fluo-4-AM loaded cells. A SOCE (F/F
0
= 1.75 ± 0.08,
n
= 47) was observed in hiPSC-CMs when the external Ca
2+
concentration ([Ca
2+
]
o
) was switched from 0 to 1 mM after SR Ca
2+
was completely depleted by caffeine (20 mM) and thapsigargin (10 µM). The SOCE was inhibited by non-selective TRPC blockers gadolinium (F/F
0
= 1.05 ± 0.03,
n
= 13) and SKF-96265 (F/F
0
= 1.04 ± 0.03,
n
= 17), respectively, compared to control (p<0.05). Whereas, the SOCE in hiPSC-CMs was significantly reduced only by pretreatment with anti-TRPC6 antibody (F/F
0
= 1.38 ± 0.06,
n
= 15, p<0.05), but not with anti-TRPC1 (F/F
0
= 1.93 ± 0.19,
n
= 8) or anti-TRPC3 antibodies (F/F
0
= 1.49 ± 0.05,
n
= 14), indicating TRPC6 channels are essential for SOCE in hiPSC-CMs. In addition, the hiPSC-CMs exhibit a property of spontaneous rhythmic beating. After SR Ca
2+
depletion, spontaneous Ca
2+
waves reappeared via refilling from the extracellular Ca
2+
source, suggesting the involvement of SOCE in the generation of spontaneous Ca
2+
waves. This idea was confirmed by the application of TRPC blockers, including gadolinium, SKF-96265 and Pyr3, all of which showed mild to potent inhibitory effects on the spontaneous Ca
2+
waves. In conclusion, we demonstrated the existence of SOCE in hiPSC-CMs. SOCE mediated by TRPC channels, especially the TRPC6, may act as an important mechanism of controlling Ca
2+
handling and arrhythmogenesis in the developing human heart.
Abstract 19641: Kv 4.3 Expression Improves Cardiac Function in Heart Failure Mice
Authors: Guilbert Arnaud , Cheng Jun , Wang Yanggan
Published: April 2024

Background:
It is known that CaMKII inhibition improves contractility in failing ventricle. However, we reported that drug and genetic CaMKII inhibition deteriorates diastolic function. We recently uncovered a mechanism that I
to
channel Kv 4.3 inhibits CaMKII activation by directly binding to the CaM binding sites. Unfortunately, this endogenous CaMKII inhibitor is down-regulated in heart failure (HF).

Objective:
We have tested whether Kv4.3 expression in HF ventricular myocytes can improve contractility without impairment of diastolic function.

Methods:
HF was induced in mice by severe aortic thoracic banding (sTAB). Kv4.3 was transfected in HF mouse left ventricle (LV) by myocardium Ad-Kv4.3 injection in the week two after sTAB. Heart function was assessed by echocardiography at the day before (day 0) and day 7 after adenovirus injection, respectively, while sarcoplasmic reticulum (SR) Ca
2+
leak, Ca
2+
transient and sarcomere shortening and relaxation were recorded in HF ventricular myocytes with Kv4.3 transfection.

Results:
HF was produced in one week after sTAB and heart function then remains stable from the post-sTAB week 2 to 5. Compared to the HF mice transfected with Ad-β-gal (control), LV myocytes transfected with Ad-Kv 4.3 showed a reduction of overall CaMKII activity by 10 ± 0.5 % with a reduction of CaMKII-dependent phosphorylation of PLB-Thr17 (13 ± 1.3 %) and RyR-2815 (10 ± 1.2 %), indicating only the localized CaMKII inhibition in the SR microdomain, consistent with the membrane distribution of Kv4.3. Kv4.3 transfection in HF mice produced a significant increase in systolic function (increased EF) and improvement of diastolic function (reduced E/E’). LV myocytes transfected with Kv4.3 showed a significant reduction of SR Ca
2+
leak, an increase in Ca
2+
transient and sarcomere shortening. Importantly, unlike drug inhibition, Kv4.3 transfected HF myocytes showed unchanged sarcomere relaxation, FDAR, and myofilament sensitivity to Ca
2+
. This is associated with an unchanged CaMKII-dependent troponin-I phosphorylation.

Conclusion:
Our results suggest that Kv4.3 expression (restoration) in failing ventricle can improve contractility without deterioration of relaxation, likely via inhibition of the compartmentalized CaMKII.
Abstract 19644: A Biocompatible Light-Activated Adhesive for Intra- and Extracardiac Applications in Acquired and Congenital Heart Disease
Authors: Lang Nora , Nunes Pereira Maria , Friehs Ingeborg , Vasilyev Nikolay , Ablasser Klemens , O'Cearbhaill Eoin , Xu Chenjie , Yamauchi Haruo , Hammer Peter , Wasserman Steve , Karp Jeffrey M , del Nido Pedro
Published: April 2024

Background:
There is a clinical need for alternative methods for tissue to tissue and device to tissue attachments in cardiovascular surgery. Tissue adhesives offer a potential solution. However, commercially available tissue adhesives are associated with poor control over adhesion and low adhesive strength, especially in the presence of blood and under dynamic conditions. Thus, we developed a light-activated adhesive, poly(glycerol-co-sebacate) acrylate (PGSA) and evaluated its effectiveness for interventions in acquired and congenital heart disease.

Methods and Results:
The adhesive strength of PGSA and cyanoacrylate (CA) coated patches was evaluated in pull-off tests using fresh myocardial tissue. In the presence of blood, adhesive strength was 1.4 ± 0.6 N/cm2 and 1.6 ± 0.3 N/cm2 for PGSA and CA coated patches, respectively. In addition, the adhesive strength did not decrease in case the PGSA coated patch was immersed in a blood-filled glass dish for 5 minutes before the measurement. To evaluate the ability of PGSA to close cardiac defects, transmural left ventricular (LV) wall defects (d=2 mm) were created in a chronic in vivo rat model and closed with a biocompatible patch and PGSA (n=26). Closure with sutures only or CA was used as a control. Animals were sacrificed after 7, 28 and 60 days. Closure was successful in over 90% of the cases for all three groups. Histology revealed a good integration of the patch with minimal inflammatory reaction. In contrast, closure with CA exhibited a pronounced inflammatory response. Echocardiography reveals preservation of LV function for PGSA whereas closure with sutures led to impaired regional contractile function. In addition, surgically created incisions in the aorta (d=1 mm, n=1) and the carotid artery (d=2 mm, n=4) were successfully closed with only PGSA without bleeding and blood flow was confirmed in an acute in vivo pig model (n=3). Histology revealed intact endothelium at the curing site and no thrombi.

Conclusions:
Cardiovascular defects can be successfully closed with a light activated tissue adhesive in a chronic animal model. Longterm evaluation indicates superiority over closure with sutures or CA. PGSA is a promising adhesive for a variety of cardiovascular applications including devices.
Abstract 19732: Low Calorie Cranberry Juice Reduces Risk Factors of Cardiovascular Disease in Adults
Authors: Novotny Janet A , Baer David J , Khoo Christina , Gebauer Sarah
Published: April 2024

Foods rich in phenolics are associated with reduced risk for cardiovascular disease. Cranberry juice is rich in a variety of phenolic compounds, including flavonoids. We conducted a double-blind, placebo controlled randomized clinical trial to investigate the effect of daily consumption of a low calorie cranberry juice beverage on risk factors of cardiovascular disease. Volunteers (n=26 men and n=30 women), aged 51+11 years, with a body weight of 79.3+8.8 kg and BMI of 28.4+4.3 (mean+SD) consumed a low calorie cranberry juice beverage or a color/flavor/calorie-matched placebo beverage as part of a controlled diet for 8 weeks. The controlled diet consisted of typical American foods, and menus were scaled to meet volunteers’ individual energy requirements such that body weight did not change during the study. Fasting blood samples were collected immediately prior to the intervention and after 4 weeks and 8 weeks of treatment. Outcome variables were compared between treatments with a mixed model ANOVA, and values at 4 weeks and 8 weeks of treatment were compared to baseline with a repeated measures ANOVA. After 8 weeks of cranberry juice beverage consumption, c-reactive protein was significantly lower compared to that after consumption of the placebo beverage (LSmeans+SEM of 2.74+0.56 mg/L for cranberry juice compared to 3.83+0.59 mg/L for placebo). Soluble ICAM-1 was also significantly lower after consumption of cranberry juice compared to placebo (LSmeans+SEM of 257.3+10.6 ng/mL for cranberry juice compared to 288.9+11.1 ng/mL for placebo). In addition, triglycerides were significantly reduced from baseline when volunteers consumed the cranberry juice (mean+SEM reduction of 14.2+5.7 mg/dL for cranberry juice compared to 1.5+4.9 mg/dL for placebo. The significant decrease in c-reactive protein, an important biomarker of inflammation and a clinically relevant risk factor for several cardiovascular diseases, suggests that cranberry juice beverage could ameliorate an underlying physiological state (inflammation) associated with risk for disease. Incorporation of a low calorie cranberry juice beverage into the diet of adults appears to reduce risk factors of cardiovascular disease.
Abstract 19760: Factors Influencing Blood Pressure Control and Therapeutic Adherence in a Comprehensive Hypertension Management Program
Authors: Sandoval Daniela , Bravo Miguel , Romero Tomás , Koch Elard , Acevedo Jhonny , HenrÍquez Oscar
Published: April 2024

Background:
Lack of life style modification counseling, poor antihypertensive drug therapy (Rx) adherence, low education, poor patient-physician relation have been described among other social determinants as hurdles in achieving blood pressure (BP) control in hypertensive patients. Objectives: This study assesses these factors in a government sponsored Cardiovascular Health Program (CHP) that provides free access to antihypertensive treatment and life style modification counseling to Chilean hypertensive population.

Methods:
From a universe of 1,512 hypertensive patients (1,069 women) between 30 y 68 years followed throughout the CHP, a sample of 349 patients was analyzed. All patients received free Rx and life style modifying counseling. Surveys of physician-patient relationship, weekly physical activity (leisure physical activity) family income and education level were carried out. Rx adherence was determined using the Morisky-Green-Levine test. Odds ratio (OR) analysis adjusted for age and sex was performed to assess the influence of these factors in BP control (<140/90 mmHg) and Rx adherence.

Results:
The mean age of the sample was 55.0 ± 8.2 years. BP control was achieved in 49.0% (741 of 1,512) of patients. 94,5% (1,429 of 1,512) received pharmacological treatment. Adherence to antihypertensive Rx was 34.9% (499 of 1,429). Factors related to BP control and influencing Rx adherence with their OR are shown in Table 1.

Conclusions:
Education, patient-physician relation, low social support and physical activity level influenced BP control. The same factors with the exception of physical activity level influenced Rx adherence that did not appear to affect decisively BP control. These results underscore the importance of social determinants and life style modification counseling implemented throughout this comprehensive hypertension management in the Chilean CHP.
Abstract 19806: Left Atrial Remodeling in Hypertrophic Cardiomyopathy and Markers for Atrial Fibrillation: Assessment by Cardiovascular Magnetic Resonance Imaging
Authors: Schwartz Robert , Haas Tammy , Browning Joseph , Lesser John , Garberich Ross , Maron Martin , Burkhoff Daniel , Maron Barry
Published: April 2024

Introduction.
Atrial fibrillation (AF) is the most common sustained arrhythmia in hypertrophic cardiomyopathy (HCM), and an important determinant of clinical deterioration due primarily to heart failure and embolic stroke

Hypothesis.
Left atrial (LA) structural and functional parameters were assessed with high resolution cardiovascular magnetic resonance imaging (CMR) to provide imaging markers associated with the risk for developing AF in HCM patients.

Methods.
We studied 438 consecutive HCM patients (age 47 17 years) with CMR, including 57 with a history of paroxysmal AF, 13 in persistent AF, 368 without AF history, as well as 244 normal controls. The LA chamber was assessed for absolute and indexed end-diastolic volume (LAEDV) and end-systolic volume (LAESV), and % ejection fraction (LAEF).

Results.
Absolute LAEDV was significantly greater in HCM patients with AF (157 ± 73 ml) than in patients without AF (109 ± 39 ml), or normal controls (80 ± 24 ml; p < 0.001). LAEF was lower in HCM with AF (34 ± 17%) than in HCM without AF (46 ± 12%) or controls (55 ± 9%; p < 0.001), and decreased progressively from control values to HCM without AF to HCM with paroxysmal AF (37 ±16 ml), and to those patients with persistent/chronic AF (18 ±13%; p < 0.001). A multivariate model showed LAEF (< 40%) and LAEDV (> 125 ml), as well as age (> 46 years) each to be independently associated with occurrence of AF. Combining these 3 CMR variables most accurately discriminated the susceptibility to AF with the area under ROC curve = 0.805, and the accuracy = 82%.

Conclusions.
In HCM, % LAEF, as assessed by CMR, is a novel marker associated with AF, and in conjunction with increased LAEDV and older age.
Abstract 20: Bystander Cardiopulmonary Resuscitation with Chest Compressions Only According to Dispatcher Telephone Instruction Status
Authors: Nagao Ken , Tachibana Eizo , Nishikawa Kei , Yagi Tukasa , Yonemoto Naohiro , Takayama Morimasa , Shirai Shinichi , Nonogi Hiroshi , Kimura Takeshi
Published: April 2024

BACKGROUND

The 2010 AHA guidelines for cardiopulmonary (CPR) recommended that untrained lay rescuers should continue chest compression-only CPR under dispatcher-telephone CPR instruction and trained lay rescuers should continue conventional CPR if he or she is able to perform rescue breaths. We assessed the effect of bystander CPR according to dispatcher-telephone CPR instruction status.

METHODS

From the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital cardiac arrest, we extracted the adult patients with bystander-witnessed out-of hospital cardiac arrest due to cardiac etiology, and divided into groups according to the dispatcher-telephone CPR instruction status, inclusive of CPR techniques. The primary endpoint was 30-day favorable neurological outcome after cardiac arrest.

RESULTS

Of the 113,624 patients who met the inclusion criteria, 45,565 received dispatcher-telephone CPR instruction and 68,059 did not. Higher proportions in the instruction group than in the no instruction group were the performance of bystander CPR (chest-compression only CPR or conventional CPR) (68% [30,929/45,565] vs. 31% [20,900/68,059], p<0.0001), especially that of chest-compression only CPR (46.2% [21,032/45,565] vs. 17.0% [11,541/68,059], p<0.0001). Although frequencies of 30-day favorable neurological outcome in the instruction group were significantly lower than in the no instruction group for the whole cohorts (4.8% vs. 5.5%, p<0.0001) and the subgroups of patients receiving bystander CPR (5.7% vs. 7.8%, p<0.0001), chest-compression only CPR was equivalent or superior to conventional CPR in each group in terms of neurological benefit (5.7% vs. 5.9% in the instruction group, p=0.57, and 8.2% vs. 7.3% in the no instruction group, p=0.03). Among patents receiving bystander CPR, adjusted odds ratios of favorable neurological outcome were 1.2 (95% CI; 1.1 to 1.3) after no instruction group, and 1.1 (1.0 to 1.2) after chest-compression only CPR.

CONCLUSIONS

Bystander chest-compression only CPR was not inferior to conventional CPR in terms of neurological benefits, and dispatcher-telephone CPR instruction increased the performance rate of chest-compression only CPR.
Abstract 206: Intravenous Lipidic Oxygen Microparticles Improve Arterial Oxygen Content and Cerebral Oxygen Delivery During CCC-Only CPR
Authors: Kheir John , Thomson Lindsay , Danforth Lauren , Cronin Julie , Dowling Catherine , Elder Jennifer , Velazquez Luis , Nadkarni Vinay , Berg Robert , McGowan Francis
Published: April 2024

Background: Although the effectiveness of CCC-only CPR is well-established, the benefits of adjuncts to further improve systemic oxygen delivery merit study. Oxygen gas can be encapsulated within injectable microparticles, or lipidic oxygen microparticles (LOMs), which transfer oxygen rapidly to the bloodstream within seconds of intravenous injection. The purpose of this study was to determine whether LOMs increase arterial oxyhemoglobin concentration, oxygen delivery and affect ROSC in a porcine model of experimentally-induced VF employing CCC-only CPR.

Methods: Yorkshire swine (30 kg) were sedated with Ketamine and Xylazine for tracheal intubation and placement of femoral venous and arterial catheters. VF was induced and animals were immediately extubated and treated as shown in Fig 1A. CPR depth, rate, and leaning was guided in all animals with real time feedback from the monitor/defibrillator. Animals with shock-refractory VF were randomized to treatment with standard ACLS therapy with (n=5) or without (n=3) intravenous LOMs (Fig 1A).

Results: Relative to controls, animals treated with LOMs in addition to standard ACLS therapy exhibited a significantly increased arterial oxyhemoglobin saturation during LOM administration (P<0.0001, 2 way ANOVA, Fig 1B), a higher cerebral NIRS during LOM administration (P<0.0001, linear regression, Fig 1C), a higher diastolic blood pressure during LOM administration (P<0.0001, linear regression, Fig 1D), and a trend towards increased incidence of ROSC (P=0.36, Fig 1E). CPR quality (depth and rate) was similar between groups (P=1.00).

Conclusion: LOMs may increase arterial oxygen content, cerebral oxygen delivery during CCC-only CPR, and may be a useful adjunctive therapy in non intubated patients with out-of-hospital cardiac arrest.