bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13051: Unbiased Estimate of Heritability of CAD Before and After Adjustment for Traditional Risk Factors in Five NHLBI Cohorts
Authors: Salfati Elias L , Li Jin , Del Gobbo Liana , Assimes Themistocles L
Published: April 2024

Introduction:
The relative contribution of traditional risk factors (TRFs) to the genesis of CAD remains uncertain. Cohort studies report a high population attributable risk for TRFs, but only a third of the GWAS loci for CAD mediate risk through TRFs. Furthermore, these loci explain a small fraction of the overall heritability of CAD based on twin studies making it unclear whether these patterns will persist and whether estimates from twin studies are inflated.

Hypothesis:
Unbiased estimates of narrow sense heritability (

h
2

) of CAD using contemporary analytic techniques applied to very distantly related individuals prior to and after adjustment of TRFs have not yet been reported. We hypothesized that such estimates would confirm a high heritability of CAD and that a substantial proportion of the genetic variance would be independent of TRFs.

Methods:
We used ~7 million genome wide imputed single nucleotide polymorphisms (SNPs) and a mixed linear model implemented in Genome-wide Complex Trait Analysis to estimate the

h
2

of CAD from genomic relatedness among participants of five prospective NHLBI cohorts - ARIC, CHS, FHS, MESA, and WHI. To guard against bias from differences in minor allele frequencies (MAF) as well as region-specific heterogeneity in linkage disequilibrium (LD) between variants used in our analyses and causal variants, we used MAF and LD stratified multicomponent genetic restricted maximum likelihood. We ran 2 models assuming a population prevalence of 8%. The first model was not adjusted for any covariates and the second was adjusted for all TRFs as well as use of antihypertensive and statin drugs.

Results:
We analyzed a total of 23,522 participants including 3520 that developed incident clinical CAD during follow up. CAD

h
2

was 39% (±3.1%) in our unadjusted model and 32% (±3.2%) in our fully adjusted model. A large majority (~95%) of the heritability in both models was derived from common SNPs with MAF >1%.

Conclusions:
CAD is a moderately heritable trait with a large fraction of its genetic variance being a result of processes unrelated to TRFs. Prior family based estimates of the

h
2

of CAD do not appear biased upwards. Consistent with many other complex traits, a majority of the genetic variance can be explained by common SNPs with very modest effects.
Abstract 13072: The 6 Minute Walk Test Improves Exercise Confidence in Chronic Heart Failure Patients
Authors: Ha Francis J , Toukhsati Samia R , Yates Rosie , Cameron James , Hare David L
Published: April 2024

Introduction:
Chronic heart failure (CHF) patients have poor adherence to self-care behaviours, particularly exercise. Patient confidence in their physical abilities is a known predictor of exercise adherence. However, factors influencing confidence are poorly understood and the efficacy of simple interventions to increase such confidence is not known. The aim of this single-site, repeated measures study was to evaluate the effects of a 6-minute walk test (6MWT) on exercise confidence in CHF patients.

Methods:
CHF patients attending an out-patient heart failure clinic at a major tertiary hospital were prospectively enrolled to perform a 6MWT under supervised conditions according to American Thoracic Society Guidelines. Consenting participants completed the Cardiac Depression Scale (CDS) at baseline and an Exercise Confidence Survey (range 0-100; higher scores indicate greater confidence) at baseline and following completion of a 6MWT. Baseline demographics, including CHF characteristics, were obtained from hospital medical records.

Results:
Fifty-seven CHF patients were eligible for enrolment to the study (81% males, mean age = 63 ± 13 years). Most patients (68%) had non-ischemic CHF aetiology and were NYHA class II or III. Over one quarter of patients (28%) were depressed (CDS ≥ 95). Baseline Total Exercise Confidence (mean 66 ± 24) was inversely associated with age (p<0.01), NYHA class (p<0.001), and depression (p<0.001). Distance walked on 6MWT (mean = 400 ± 123 metres) was positively correlated with Baseline Total Exercise Confidence (p<0.001) and with each of the baseline Exercise Confidence sub-scales (ie., Walking, Running, Climbing and Lifting Confidence; p<0.001). Following the 6MWT, a significant improvement in Total Exercise Confidence (F
(
1, 49)
= 7.26, p<0.01) and Running Confidence (F
(1, 51)
= 4.77, p<0.05) adjusted for age, CDS score and NYHA class, was observed.

Conclusions:
These findings suggest that the 6MWT is a simple and effective intervention to improve exercise confidence in chronic heart failure patients. These results may have important patient self-management implications; future research should monitor whether improvements in exercise confidence are persistent and translate to changes in exercise behaviours.
Abstract 13075: Histopathological Analysis of Two Major Ascending Aortopathies: Implication of Vasa Vasorum Degeneration in Their Pathogenesis
Authors: Osada Hiroaki , Meshii Katsuaki , Kato Kaori , Kanemitsu Naoki , Kyogoku Masahisa
Published: April 2024

Introduction:
Aortic medial weakness is a major predisposing factor in the development of aortic dissection or aortic aneurysm. Impaired vasa vasorum (VV) or venous vasa vasorum (VVV) function may induce hypoxia and malnutrition, possibly resulting in aortic medial weakness.

Hypothesis:
We hypothesized that the start of ascending aortopathy could be identified by histopathological analysis.

Methods:
We retrospectively evaluated 69 consecutive patients (28 men, 41 women; mean age 68.2 ± 12.1 years) who underwent ascending aortic repair from 2008 to 2015. The patients were divided into group AD (type A aortic dissection, n=47 ) and group AA (ascending aortic aneurysm, n=22). We evaluated patient characteristics and graded VV/VVV degeneration of the adventitia (none = 0, trivial = 0.5, mild = 1, moderate = 1.5, severe = 2) regarding elastoma formation, smooth muscle cell proliferation, myomatous change, and sclerosis.

Results:
There were no significant differences between the two groups regarding age, sex, body surface area, history of hypertension, or diameter of the ascending aorta before surgery. Four patients in group AD had gene-related aortic dissection (Marfan syndrome, three patients; bicuspid aortic valve, one patient). Nine patients in group AA had a bicuspid aortic valve. There were significant differences between the two groups in regard to smooth muscle cell proliferation [VV (group AD: 1.40 ± 0.49 points; group AA: 0.98 ± 0.19 points; p<0.001); VVV (group AD: 1.40 ± 0.55 points, group AA: 1.04 ± 0.51 points, p=0.013] and total degeneration score (VV: group AD: 3.17 ± 1.42 points, group AA: 2.39 ± 1.41 points, p=0.036). There were no significant differences between the two groups regarding myomatous change or sclerosis.

Conclusions:
Degeneration of the VV and, especially, smooth muscle cell proliferation of the VV and VVV appear to be responsible for aortic dissection. Elucidation of the smooth muscle degeneration pathway may lead to identifying the turning point at which aortic wall weakness induces dissection or enlargement.
Abstract 13083: Anatomy Characterization Informs Implant Procedure Design for a Novel Extravascular ICD System
Authors: Lahm Ryan , Bhatia Varun , Harris Megan
Published: April 2024

Introduction:
Extravascular approaches to ICD therapy in some clinical situations require unique implant methods. Current systems require high energy and don’t provide anti-tachycardia pacing. A new extravascular approach involves placement of a defibrillation lead between the heart and sternum. Due to the unfamiliarity most ICD implanters have with this space, quantification of the anatomy there is crucial for development of a safe and effective procedure.

Methods:
CT scans were segmented and analyzed to characterize relative locations of structures in or near the substernal space including heart, lungs, sternum, and mammary arteries. Segmentation resulted in faceted 3D surface models. A lead was virtually implanted behind the sternum in the intended location. Proximity distributions from the lead to various structures in the space were characterized at multiple levels of the sternum (up to the 3
rd
intercostal space (ICS)). Additionally, the location along the right ventricular (RV) long axis where the lead was closest to the heart was measured.

Results:
Analysis was completed in 68 patients. The myocardium was closest on average to the virtual lead at the level of the xiphisternal junction (Fig. 1)(5
th
- 95
th
percentile: 1.0 - 9.9 mm) and furthest away at the 3
rd
ICS (4.2 - 47.5 mm). It was closest to lung tissue at the 3
rd
ICS (1.2 -14.7 mm) and furthest away at the tip of the xiphoid process (20.7 - 73.9 mm). The mammary arteries were found to be no closer than 11.5 mm to either margin of the sternum at any level. At the xiphisternal junction, the lead sat at ~60% along the RV long axis (0%=RV apex, 100%=tricuspid valve), suggesting close proximity to the central portion of the RV.

Conclusions:
Meaningful variation exists in the geometric relationships between many of the anatomical structures of the substernal space. Despite this variation, these results support that a lead can be placed in the substernal space close to myocardium while avoiding other organs.
Abstract 13089: Evidence That Loss of Nuclear-Encoded Mitochondrial Gene Activity in the Arterial Wall Relates to Atherosclerotic Lesion Development
Authors: Vilne Baiba , Skogsberg Josefin , Foroughi Asl Hassan , Kessler Thorsten , Björkegren Johan L , Schunkert Heribert
Published: April 2024

Introduction:
Besides acting as “power houses” of the cell, mitochondria also serve as sensors of their local environment and are intimately involved in cellular defense.

Hypothesis:
Dysregulation of nuclear-encoded mitochondrial (NEM) genes might represent an intermediate step by which hypercholesterolemia imposes the development of atherosclerotic lesions.

Methods and Results:
In order to test this hypothesis, we examined the transcriptome of the aorta in Ldlr
–/–
Apob
100/100
Mttp
flox/flox
Mx1-Cre at 10 week intervals by applying a number of in silico systems biology strategies. In parallel to the rapid atherosclerotic lesion expansion and foam cell formation, i.e. between 30 and 40 weeks of age, we observed that NEM genes were 4-fold down-regulated compared to all other genes (P=6.1x10
–72
). This down-regulation involved PGC1-α and -β, two members of the peroxisome proliferator-activated receptor γ co-activator 1 family of transcription regulators. In addition, when studying the correlation of gene co-expression modules with mouse phenotypic traits, we identified two NEM gene-enriched modules as being the most negatively associated with changes in atherosclerotic lesion size (r= -0.42 and -0.43, P=0.04). Within these two modules, gene-set enrichment analysis revealed significant over-representation of transcription factor estrogen related receptor (ERR) α binding sites, ROS-sensitive genes, as well as several mitochondrial biogenesis-related signaling pathways. ERR-α is a known effector of PGC1 in the control of mitochondria biogenesis and antioxidant defense and, in our data, its expression tightly correlated with that of PGC1 factors. Further- more, human data revealed that both modules demonstrated significant enrichment for CAD GWAS SNPs associated with arterial wall (3.3-fold P<6.1x10
–19
) and blood (1.4-fold, P<8.1x10
–9
) gene expression, implying a causative role in atherosclerosis development. Finally, genetic lowering of plasma cholesterol at 30 weeks resulted in 4-fold up-regulation of NEM genes in the aorta of Mttp
Δ/Δ
mice (P=3.9x10
–16
).

Conclusions:
The arterial wall in mice responds to hypercholesterolemia by a coordinated and reversible down-regulation of NEM genes which affects atherosclerosis development.
Abstract 13104: Small Molecules Prevent Thrombin Induced Rho-Rock-MLC Mediated Hyperpermeability in Endothelial Cells
Authors: Samanta Saheli , Rajasingh Sheeja , Patel Urmi , Cao Thuy , Dawn Buddhadeb , Rajasingh Johnson
Published: April 2024

Introduction:
Thrombin, a serine protease plays an important role in a wide array of a normal and pathological process, including infection, inflammation and tissue injury. There are limited numbers of molecules that prevent vascular inflammation and injury during ALI or ARDS. Our novel combination therapy with epigenetic modifiers that could target the genes epigenetically to reduce thrombin induced hyperpermeability and injury. Here, we use 5-Aza 2-deoxycytidine (Aza) and Trichostatin A (TSA) together to see the restoration of throbin-induced hyperpermeability.

Hypothesis:
We hypothesize that treatment with the combination Aza and TSA (Aza+TSA) will restore the thrombin induced vascular hyper permeability and increases vascular integrity.

Methods and Results:
In thrombin induced vascular hyperpermeability, the epigenetic modifiers Aza or TSA alone cannot be able to circumvent the inflammation and restores the cell integrity. However, the Aza+TSA treatment showed a significant level of decrease in vascular hyperpermeability and promoted survival rate. Our Western analysis data suggest that the combination of Aza+TSA treatment suppressed phosphorylation of MLC and ROCK and also Rho1. ROCK-mediated phosphorylation of MLC results in increased actin-filament assembly and actomyosin contraction, which is evident to stress fiber’s formation (Fig. 1A). This was further supported by the immunofluorescence analysis (Fig. 1B).

Conclusions:
Our data shows that Aza+TSA prevents thrombin induced endothelial hyperpermeability through the inhibition of Rho-ROCK-MLC pathway. Thus Aza+TSA has a substantial therapeutic value during infection, inflammation and acute lung injury.
Abstract 13118: Urinary Sodium and Potassium Excretion are Associated With Blood Pressure among Adults in the United States
Authors: Jackson Sandra L , Cogswell Mary E , Zhao Lixia , Coleman King Sallyann M , Chen Te-Ching , Terry Ana L , Wang Chia-Yih , Wright Jacqueline , Loria Catherine M , Merritt Robert , Bowman Barbara
Published: April 2024

Introduction:
One in three US adults has hypertension, a major risk factor for cardiovascular disease. We aimed to assess the associations between 24-h urinary excretion of sodium, potassium, and sodium-potassium ratio with blood pressure and hypertension status among US adults.

Hypothesis:
We hypothesized that urine sodium excretion and urine sodium-potassium ratio would be positively and urine potassium excretion would be inversely associated with blood pressure and hypertension.

Methods:
Cross-sectional data on up to two 24-h complete urine collections were analyzed from 765 non-institutionalized participants aged 20-69 y in the 2014 US National Health and Nutrition Examination Survey (NHANES). Urine collection started and stopped in the NHANES mobile examination center. Approximately half of participants had two complete collections; usual sodium and potassium excretion, and sodium-potassium ratio, were estimated using measurement error models accounting for day-to-day variability. Analyses adjusted for age, sex, race/ethnicity, body mass index, history of cardiovascular disease, diabetes, chronic kidney disease, smoking status, and physical activity, as well as the complex survey design.

Results:
In fully adjusted linear regression models, sodium excretion was positively associated with systolic (4.43 mmHg per 1000 mg/day, 95% CI 2.31,6.56) and diastolic (1.93 mmHg, 95% CI 0.34,3.51) blood pressure. Sodium-potassium ratio was also positively associated with systolic blood pressure (2.86 mmHg per .5 unit increase, 95% CI 1.15,4.56), and potassium excretion was inversely associated with systolic blood pressure (-3.39 mmHg per 1000mg/day increase, 95% CI -6.05,0.72). Adjusted odds ratios for hypertension, for excretion in the highest compared to the lowest quartiles, were 4.34 (95% CI 1.37,13.79) for sodium and 0.39 (95% CI 0.17,0.88) for potassium. Results were robust in sensitivity analyses restricted to persons not taking antihypertensive medications.

Conclusions:
Using a nationally-representative sample of US adults and a “gold-standard” urine biomarker, these data further support the strong relationship of higher sodium and lower potassium excretion with higher blood pressure and hypertension risk.
Abstract 13129: Acute Inhibition of Sodium Channel Beta Subunit (β1) -mediated Adhesion is Highly Proarrhythmic
Authors: Veeraraghavan Rengasayee , Hoeker Gregory S , Poelzing Steven , Gourdie Robert G
Published: April 2024

Introduction:
The sodium channel auxiliary subunit and cell adhesion molecule β1 (SCN1b) is enriched at cardiomyocyte intercalated disks (ID) along with the pore-forming subunit Na
V
1.5. We recently demonstrated that the perinexus, an Na
V
1.5-rich ID nanodomain located near connexin43 (Cx43) gap junctions (GJ), is important for cell-to-cell electrical coupling. Disrupting close membrane apposition within the perinexus was highly proarrhythmic.

Hypothesis:
β1-mediated adhesion is key to close membrane apposition within the perinexus; therefore, inhibiting β1-mediated adhesion may disrupt perinexal structure, impair conduction and precipitate arrhythmias.

Methods and Results:
Na
V
1.5 and β1 localization within ID nanodomains was quantitatively assessed from super-resolution STochastic Optical Reconstruction Microscopy (STORM) images of
en face
IDs from adult guinea pig ventricles. Na
V
1.5 and β1 were located 63±15 and 75±25 nm from Cx43 GJ; 31% of both Na
V
1.5 and β1 localized to GJ perinexi. β1-mediated adhesion was acutely inhibited by βadp1, a novel peptide mimetic of β1’s putative extracellular adhesion domain. βadp1 decreased cellular adhesion as assessed by Electric Cell-Substrate Impedance Spectroscopy (ECIS) in β1-overexpressing 1610 cells in a dose-dependent manner but not in native 1610 cells. Perinexal intermembrane spacing as measured by Transmission Electron Microscopy (TEM) increased 3-fold from 17±1 nm in vehicle controls (0.25% DMSO) to 49±5 nm (p<0.05) in 100 μM βadp1-treated hearts; however, intermembrane spacing at other ID locations was unaltered (22±1 vs. 24±1 nm). Optical mapping revealed preferential slowing of transverse conduction (8.0±0.7 vs. 16.5±1.2 cm/s, p<0.05) and increased anisotropy (3.9±0.2 vs. 2.6±0.2, p<0.05) in βadp1-treated hearts relative to vehicle controls. Further, 3 of 4 βadp1-treated hearts exhibited spontaneous ventricular tachycardias.

Conclusions:
These data support a role for β1-mediated adhesion in maintaining close apposition between Na
V
1.5-rich perinexal membranes. Importantly, acute inhibition of β1-mediated adhesion resulted in disruption of close membrane apposition within the GJ perinexus and precipitated severe conduction slowing and spontaneous arrhythmias.
Abstract 13132: Evolving Heart Block treated With a CHOP
Authors: Zein Rami K , Mouabbi Jason A , Inany Mohammed , Hadid Tarik , Lalonde Thomas
Published: April 2024

Introduction:
Primary cardiac lymphoma (PCL) is a very rare disorder accounting for less than 1% of all lymphomas. Presenting symptoms may be chest pain, congestive heart failure, pericardial effusions and arrhythmias. Herein, we present the case of a 62- year-old immunocompetent female with a one week history of worsening endurance and Wenckebach heart block who was ultimately diagnosed with primary cardiac lymphoma.

Case:
A 62-year-old woman was admitted with dyspnea, fatigue and bilateral pitting edema for 1 week. She was bradycardic with a heart rate of 55. Clinical examination was otherwise unremarkable. Electrocardiogram demonstrated Mobitz I second degree AV block. Echocardiography subsequently revealed a right atrial and ventricular mass. CT angiography of the chest demonstrated a 4-5 centimeter filling defect surfacing from the posterior right atrial and ventricular wall. She subsequently developed complete AV block with runs of ventricular tachycardia during her hospitalization requiring biventricular pacemaker implantation with automatic defibrillator. Excisional biopsy revealed diffuse large B-cell lymphoma. Patient underwent 6 cycles of rituximab, cyclophosphamide, adriamycin, vincristine and prednisone (R-CHOP) and achieved complete remission.

Discussion:
PCL often presents with non-specific symptoms that vary depending on the locations in the myocardium. The most common clinical manifestations are pericardial effusion, AV block and heart failure being the most common cause of death. Imaging studies are essential in estimating the extent of disease. However, surgical intervention is needed to confirm the diagnosis histologically. Fortunately, early treatment with R-CHOP can lead to remission. This case represents a fascinating presentation of a very rare malignancy.
Abstract 13136: Physically Frail Adults With Heart Failure Have Worse Physical and Affective Symptoms
Authors: Denfeld Quin E , Mudd James O , Winters-Stone Kerri , Hiatt Shirin O , Gelow Jill M , Chien Christopher V , Lee Christopher S
Published: April 2024

Introduction:
Heart failure (HF) is a complex clinical syndrome associated with significant symptom burden; however, our understanding of the relationship between symptoms and physical frailty in HF is limited.

Hypothesis:
There is a significant relationship between physical frailty and symptoms among adults with HF.

Methods:
A sample of adults with symptomatic HF were enrolled in a cross-sectional study. Physical frailty was measured according to the five dimensions of the Frailty Phenotype Criteria: shrinking, weakness, slowness, physical exhaustion and low physical activity. Physical symptoms were measured with the HF Somatic Perception Scale-Dyspnea subscale, the Epworth Sleepiness Scale, and the Brief Pain Inventory short form. Affective symptoms were measured with the Patient Health Questionnaire-9 and the Brief Symptom Inventory-Anxiety scale. Generalized linear modeling was used to quantify associations between physical frailty and symptoms, controlling for Seattle HF Model (SHFM) score.

Results:
The mean age of the sample (
n
= 50) was 57.5±9.7 years, 66% were male, 92% had New York Heart Association class III/IV HF, and 66% had non-ischemic etiology. Half of the sample (50%) had physical frailty. Those with physical frailty had more than twice the level of dyspnea (
p
= 0.001), 73% worse wake disturbances (
p
< 0.001), and 86% worse depressive symptoms (
p
= 0.001) compared with those not physically frail, adjusting for SHFM score. There were no differences in pain or anxiety.

Conclusions:
Physically frail adults with HF have considerably worse dyspnea, wake disturbances, and depression. Targeting physical frailty may help identify and improve physical and affective symptoms in HF.
Abstract 13178: A Novel, Data-Driven Approach to Classify Critical Left Ventricular Outflow Tract Obstruction Using Pre-Intervention Echocardiographic Measurements: A Report From The Congenital Heart Surgeons’ Society Data Center
Authors: Meza James M , Slieker Martijn , Mertens Luc , Blackstone Eugene H , Eghtesady Pirooz , Pourmoghadam Kamal , Kirklin James K , DeCampli William M , Jacobs Marshall , Karamlou Tara , Burch Phillip T , Karimi Mohsen , Pearl Jeffrey , Fuller Stephanie , Mascio Christopher , McCrindle Brian W
Published: April 2024

Objective:
Critical left ventricular outflow tract obstruction (LVOTO) has been traditionally classified by aortic and mitral valvar pathology. We aimed to determine if baseline qualitative and quantitative echocardiographic measures alone could define new groups of patients with greater clinical relevance.

Methods:
Pre-intervention transthoracic echocardiograms for 651 neonates with Critical LVOTO were interpreted by one pediatric cardiologist according to a standardized protocol. Cluster analysis, with 136 echocardiographic measures, was used to group the patients. Variables defining each group were identified by multinomial regression.

Results:
Cluster analysis categorized the 651 neonates into groups of 215 (Group 1), 338 (Group 2), and 98 (Group 3) patients (Panel A). Aortic valve atresia and left ventricular (LV) end diastolic volume were identified as significant discriminating variables. LV size was largest in Group 3 and smallest in Group 2. Aortic atresia was most prevalent in Group 2 and least prevalent in Group 3. The distribution of these and other variables is shown in Panel B. Balloon valvotomy was the first intervention in 9% (19/215), 2% (6/338), and 61% (60/98) (p<0.0001). In those with an initial operation, single ventricle palliation was performed in 90% (176/215), 98% (326/338), and 58% (22/38) (p<0.0001). Overall mortality in each group was 27% (59/215), 41% (138/338), and 12% (12/98) (p<0.0001).

Conclusions:
Using a completely data-driven approach, we identified three novel groups, primarily based on baseline LV size, that correlate with management strategy and overall mortality. These groups roughly correspond anatomically with multi-level LV hypoplasia, hypoplastic left heart syndrome, and critical aortic stenosis, respectively. Our analysis suggests that a more useful classification of critical LVOTO may require more detailed measurements, especially of LV size, than a simplistic scheme limited to valvar pathology.
Abstract 13201: Increase in Bystander Cardiopulmonary Resuscitation in Sweden During the Last 15 Years is Mainly Attributed to Increased Rates of “Chest Compression Only” CPR
Authors: Riva Gabriel , Hollenberg Jacob , Svensson Leif , Ringh Mattias , Rubertsson Sten , Nordberg Per , Claesson Andreas , Djärv Therese , Herlitz Johan
Published: April 2024

Introduction:
Bystander cardiopulmonary resuscitation (CPR) traditionally consists of both ventilations and chest compressions. The concept of Compression Only CPR (CO-CPR) has emerged since rescue breaths are difficult to perform, potentially delay the start of CPR, and interrupt chest compressions. Since 2010 guidelines suggest CO-CPR for untrained bystanders and for trained bystanders unwilling or unable to perform rescue breaths.

Aim:
The aim was to describe changes in rates of bystander CPR, CO-CPR and survival during 3 different time-periods of CPR-guidelines on a national level. We hypothesized that dissemination of CO-CPR would be associated with increased CPR-rates and similar survival compared to standard CPR.

Method:
A registry based cohort study including all bystander witnessed cases of out-of-hospital cardiac arrests reported to the Swedish Cardiac Arrest Registry in 2000 - 2014. Exposure was categorized as bystander CPR or No-CPR. Bystander CPR was further categorized into Standard CPR (S-CPR) or CO-CPR. Primary outcome was 30-day survival.

Results:
23169 patients were included. Total rates of bystander CPR increased from 38% in 2000-2005 to 70% in 2011-2014. CO-CPR increased from 5% in 2000-2005 to 28% in 2011-2014. There was no significant difference in survival among patients receiving CO-CPR or S-CPR (13,6% vs. 12,9% p=0,3).

Conclusion:
The increase in bystander CPR during the last 15 years in Sweden is mainly attributed to an increase in CO-CPR. Any form of bystander CPR was associated with increased 30-day survival compared to no CPR in all time periods studied. Overall 30-day survival was not different when comparing CO-CPR to S-CPR.
Abstract 13206: Culprit and Non-Culprit Recurrent Ischemic Events in Post-Myocardial Infarction Patients: Data From SWEDEHEART
Authors: Varenhorst Christoph , Johansson Saga , Hasvold Pål , Janzon Magnus , Albertsson Per , Leosdottir Margret , Hambraeus Kristina , James Stefan , Jernberg Tomas , Svennblad Bodil , Lagerqvist Bo
Published: April 2024

Introduction:
Long-term disease progression post myocardial infarction (MI) is inadequately understood and recurrences appear at the stented lesion or in untreated progressive lesions.

Hypothesis:
We studied the pattern and angiographic properties (culprit/non-culprit) of recurrent-MI (re-MI) in a large real-world patient population.

Methods:
We performed a prospective cohort study in 99,546 first-occurrence MI patients enrolled in Swedish Web system for Enhancement and Development of Evidence-based care in Heart disease Evaluated According to Recommended Therapies (SWEDEHEART) between 1 Jan 2006 and 31 Dec 2014.

Results:
A culprit lesion could be identified in 41,006 patients who underwent coronary angiography. Of those, 2,361 patients suffered a re-MI where the angiography could detect the infarct origin: 587 originated from the culprit lesion- and 1,774 from the non-culprit lesion. The cumulative event probability for re-MI within 8 years (estimated by Kaplan-Meier) related to the culprit lesion was 0.027 (0.023-0.030) as compared with 0.080 (0.075-0.085) for a non-culprit lesion (Figure).

At the index infarction, patients with subsequent culprit vs. non-culprit re-MIs were overall similar according to baseline characteristics: gender (men: 69% vs. 72%), age (66 vs. 65 years), infarction type (STEMI: 54% vs. 52%), diabetic status (22% vs. 21%), current smoking (32 % vs. 30 %), hyperlipidemia (statin treatment: 20 vs. 23 %) and hypertension (44.1% vs. 47.5%). Patients with culprit re-MIs were somewhat less likely to have 3-vessel disease at index (12% vs 17%) but procedural characteristics such as number of stents, total stent length and mean stent diameter were similar between groups.

Conclusions:
In a large cohort of first-occurrence MI patients undergoing PCI, the risk of reinfarction not originating from a previously stented lesion was three times higher than the risk of lesions originating from a previously stented lesion.
Abstract 13213: Sex-related Differences in Symptom Status Among Patients With Atrial Fibrillation
Authors: Blum Steffen , Muff Christoph , Ammann Peter , Erne Paul , Moschovitis Giorgio , Di Valentino Marcello , Shah Dipen , Schläpfer Jürg , Fischer Andreas , Merkel Tamara , Kühne Michael , Sticherling Christian , Osswald Stefan , Conen David
Published: April 2024

Background:
Many patients with atrial fibrillation (AF) have symptoms related to the arrhythmia, but little is known about sex-specific differences. We therefore prospectively assessed sex-specific differences in health perception, overall symptom status and a comprehensive panel of specific symptoms in a large cohort of AF patients.

Methods:
We performed a prospective multicenter observational cohort study of 1550 AF patients, who were enrolled between 2010 and 2014. All patients completed questionnaires about personal characteristics, co-morbidities and symptoms on a yearly basis.

Results:
Mean age was 70±11 years among women and 67±12 years among men. Health perception on a visual analogue scale was significantly lower in women than in men (67±20 vs. 72±18 respectively; p< 0.0001). Compared to men, more women had any symptoms (85.0% vs. 68.3%; p< 0.0001), palpitations (65.2% vs. 44.4%; p< 0.0001), dizziness (25.6% vs. 13.5%; p< 0.0001), dyspnea (35.7% vs. 21.8; p< 0.0001) and fatigue (25.3 vs. 19.1; p= 0.006). One year after baseline, symptoms decreased in both sexes, but remained more frequent in women (49% vs. 33%, p< 0.0001). These findings persisted after two years (48% vs. 32%, p< 0.0001) and after three years (41% vs. 31%, p= 0.02). After multivariable adjustment, female sex remained an independent predictor for a lower health perception (ß = -5.4 [95% confidence (CI) -7.4; -3.3] p< 0.0001), any symptoms (odds ratio (OR) 3.0 [95%CI 2.2; 4.1] p< 0.0001), palpitations (OR 2.8 [95%Cl 2.2; 3.7] p< 0.0001), dizziness (OR 2.3 [95%Cl 1.7; 3.1] p< 0.0001), dyspnea (OR 2.0 [95%Cl 1.5; 2.6] p< 0.0001) and fatigue (OR 1.7 [95%Cl 1.3; 2.3] p< 0.0001). Similar results were obtained one year after baseline (follow-up) as presented in the Table.

Conclusions:
Women with AF had a substantially higher symptom burden and a lower health perception than men. These relationships persisted after comprehensive multivariable adjustment and during prospective follow-up.
Abstract 13236: Elevated Serum Proprotein Convertase Subtilisin/Kexin Type 9 Level Independently Predicts Long-Term Cardiovascular Outcomes in Patients With Chronic Coronary Artery Disease
Authors: Sakamoto Aiko , Ishizaka Nobukazu , Uehara Masae , Ando Jiro , Komuro Issei
Published: April 2024

Background:
Proprotein convertase subtilisin/kexin type 9 (PCSK9) may directly promote atherosclerosis. However, the long-term impact of elevated serum PCSK9 levels on the risk of cardiovascular events has not been fully elucidated. We therefore analyzed the association of serum PCSK9 levels with major adverse cardiovascular events (MACE) in patients with chronic coronary artery disease (CAD).

Methods:
Serum PCSK9 levels were measured in 306 patients (171 men; mean age, 68.3 ± 10.5 years) who underwent coronary computed tomography (CT) angiography. Furthermore, 174 patients who were judged to have obstructive CAD were followed-up for a median period of 1584 days (interquartile range [IR] 1334-1790). MACE was defined as death, acute coronary syndrome, and cerebral stroke.

Results:
Serum levels of PCSK9 were higher in women (268 ng/mL, IR 211-325) than in men (218 ng/mL, IR 175-284, P<0.001). In age- and gender-adjusted logistic regression analysis, serum PCSK9 levels had a significant association with obstructive CAD (odds ratio 1.63 per 100 ng/mL increase, 95% confidence interval [CI] 1.21-2.19, P=0.001). Among patients with obstructive CAD, 14 patients developed MACE during the follow-up period. Patients in the highest tertile of PCSK9 (≥288 ng/mL) had a significantly higher risk of MACE than those in the lower tertiles (log-rank, P=0.005). In Cox regression analysis using age, gender, estimated glomerular filtration rate (eGFR), hypertension, dyslipidemia, diabetes, smoking, and vulnerable coronary plaque characteristics assessed by CT, including low-density plaque, positive remodeling, and spotty calcification, as covariates, serum PCSK9 level was an independent predictor of MACE (hazard ratio 2.03 per 100 ng/mL increase, 95% CI 1.13-3.62, P=0.017).

Conclusions:
Baseline serum PCSK9 level significantly predicted MACE, as well as present coronary stenosis, independent of traditional cardiovascular risk factors and vulnerable plaques.
Abstract 13237: Placental Growth Factor as a Predictor of Long-term Outcome in Patients With Acute Decompensated Heart Failure
Authors: Nakada Yasuki , Kawakami Rika , Ueda Tomoya , Nakano Tomoya , Kawata Hiroyuki , Okura Hiroyuki , Saito Yoshihiko
Published: April 2024

Background:
Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF), contribute to atherogenesis through vascular inflammation and plaque destabilization. We reported high PlGF levels (≥14.5 pg/ml) were independent predictor of adverse events in patients with chronic kidney disease, but the significance of PlGF in acute decompensated heart failure (ADHF) patients was not clear.

Methods:
We have studied consecutive 437 patients with ADHF admitted to our hospital from 2011.4 through 2014.12. Among these patients, 281 patients measured PlGF levels were studied. The primary endpoint was all-cause death.

Results:
To investigate the impact of PlGF levels on prognosis of ADHF, we divided patients into 2 groups according to previous cutoff levels (14.5 pg/ml). There was no significant differences in age, left ventricular ejection fraction, and estimated glomerular filtration rate between high PlGF group (≥14.5 pg/ml, n=49) and low PlGF group (<14.5 pg/ml, n=232). Kaplan-Meier analysis revealed that the patients with high PlGF group had worse prognosis than those with low PlGF group (p=0.0092) (Figure 1). Multivariate analysis revealed that PlGF was independent predictor of all-cause death (HR 1.026 [1.005-1.045], p=0.0172) (Figure 2).

Conclusions:
The high placental growth factor levels at acute phase in patients with acute decompensated heart failure predicts the long-term clinical outcome independent from various prognostic factors.
Abstract 13241: Additive Predictive Value of Strain Rate Dispersion Index for Responses to Cardiac Resynchronization Therapy: Substudy From the START Study
Authors: Iwano Hiroyuki , Yamada Satoshi , Okada Kazunori , Hayashi Taichi , Tsujinaga Shingo , Yokoyama Shinobu , Nakabachi Masahiro , Nishino Hisao , Ichikawa Ayako , Abe Ayumu , Kaga Sanae , Mikami Taisei , Tsutsui Hiroyuki
Published: April 2024

Background:
Response to cardiac resynchronization therapy (CRT) depends not only on the degree of mechanical dyssynchrony but on that of discoordination, which could associate with insufficient predictive value of the parameters of mechanical dyssynchrony for the response especially in patients with moderately prolonged QRS duration and/or ischemic heart disease. We thus investigated an additive predictive value of strain rate dispersion index (SRDI), an index of the amount of discoordination, in patients undergoing CRT in a multicenter study.

Methods:
We studied 180 patients included in the Speckle Tracking Imaging for the Assessment of Cardiac Resynchronization Therapy (START) study, a prospective multicenter cohort study in Japan. Time from QRS to first peak of strain (T
first
) was measured and its standard deviation (SD) was calculated as a dyssynchrony parameter for longitudinal (L-T
first
-SD) and circumferential (C-T
first
-SD) strains. SRDI was calculated as the average of segmental peak systolic strain rates minus peak global strain rate for longitudinal (L-SRDI) and circumferential (C-SRDI) strain rates. Responses to CRT was defined as a reduction of left ventricular end-systolic volume >15% at 6 months after CRT.

Results:
One-hundred and nine (61%) patients were identified as responders. By Cox proportional hazards model, the addition of SRDIs resulted in a significant incremental improvement in the predictive value for the CRT response on LV end-diastolic volume (EDV) at baseline, QRS duration, ischemic etiology, and T
first
-SDs (Chi square: 41.0 vs 59.0, P<0.001) in overall patients. Moreover, the same results were observed regardless of QRS duration or ischemic etiology (
Figure
).

Conclusion:
SRDI had an additive predictive value of responses to CRT even in patients with moderately prolonged QRS duration and those with ischemic heart disease.
Abstract 13243: Pericardial Fat is a Useful Predictor of Future Cardiovascular Events Independent of High-Risk Coronary Plaques
Authors: Sakamoto Aiko , Uehara Masae , Ishizaka Nobukazu , Ando Jiro , Komuro Issei
Published: April 2024

Background:
Pericardial fat is recognized as a risk factor for coronary stenosis. However, it remains unclear whether ectopic fat deposition, such as pericardial fat and intrathoracic fat, is an independent predictor of future cardiovascular events.

Methods:
We measured pericardial fat volume (PFV) and intrathoracic fat volume (IFV) in 355 patients (203 men; mean age, 68.1 ± 10.6 years) who underwent coronary computed tomography angiography. Among 200 patients who were judged to have obstructive coronary artery disease (CAD), cardiovascular events, defined as death, acute coronary syndrome, cerebral stroke, heart failure, and coronary revascularization, were assessed at 5 years.

Results:
There was a strong association between PFV and IFV (R=0.707, P<0.001). Body mass index (BMI) was significantly associated with PFV (R=0.538, P<0.001) and IFV (R=0.633, P<0.001). PFV and IFV were significantly larger in patients with high-risk coronary plaque (HRP), including low-density plaque, positive remodeling, and spotty calcification, than in those without (PFV, 106 mL [interquartile range, IR 80-144] vs. 85 mL [IR 61-112], P<0.001; IFV, 110 mL [IR 68-158] vs. 90 mL [IR 55-123], P=0.006). Among patients with obstructive CAD, 38 patients developed a cardiovascular event during 5 years. Patients with PFV of median or greater (≥110 mL) had a significantly higher risk of events than those with PFV below median (P=0.025). Patients with IFV of median or greater (≥118 mL) had a higher risk of events than those with IFV below median (P=0.047). When age, gender, BMI, HRP, PFV, and IFV were included in a Cox regression model, PFV, but not IFV, was a significant predictor of cardiovascular events (hazard ratio 3.02 per 100 mL increase, 95% confidence interval 1.26-7.26, P=0.014).

Conclusions:
PFV was predictive of cardiovascular events independent of other obesity parameters and HRP, indicating that pericardial fat may have local effects on the development of cardiovascular disease.
Abstract 13277: A Unique Network Involving Cxcr4 and Cxcr7 Coordinates Cardiac Lineage Specification and Mobilization of Induced Pluripotent Stem Cells
Authors: Ceholski Delaine K , Tumbull Irene C , Jarrah Andrew A , Kho Changwon , Lee Ahyoung , Hadri Lahouaria , Costa Kevin D , Hajjar Roger J , Tarzami Sima T
Published: April 2024

Introduction:
An adult heart has an intrinsically limited capability to regenerate damaged myocardium. Human embryonic and induced pluripotent stem cell (hESC/hiPSC)-based therapies offer a unique strategy for developing cell replacement treatments for numerous disorders including cardiac diseases.

Hypothesis:
The present study identifies a unique signaling network, SDF-1/CXCR4/CXCR7, that regulates cardiac lineage differentiation and migration in human induced pluripotent stem cells (hiPSCs). The fact that SDF-1 binds to CXCR4 and CXCR7 raises a concern how to distinguish the potential contribution of the SDF-1/CXCR7 pathway from SDF-1/CXCR4 pathway in all the processes that were previously attributed to SDF-1/CXCR4. Therefore, we set these studies to disseminate the role of the SDF-1/CXCR4/CXCR7 network in cardiogenic lineage differentiation and migration of hiPSCs with the premise that their improved recruitment could translate into therapeutic benefits.

Methods:
Using lentiviral vectors to ablate CXCR4 and/or CXCR7 expression, hiPSC-derived cardiomyocytes (hiPSC-CMs) were tested for phenotypic and functional properties due to gene knockdown.

Results:
Gene expression confirmed cardiomyocyte phenotype of differentiated hiPSCs, although reduction of CXCR4 and CXCR7 expression resulted in delayed cardiac phenotype. Only knockdown of CXCR4 reduced the spontaneous beating of hiPSC-CMs. Knockdown of CXCR4 and CXCR7 differentially altered calcium transients and β -adrenergic response in hiPSC-CMs. In engineered cardiac tissues, depletion of CXCR4 or CXCR7 had opposing effects on developed force. The transendothelial migration response to SDF-1 was suppressed by knockdown of either CXCR4 or CXCR7. In contrast, in a trans-well chemotaxis assay, only depletion of CXCR4 reduced hiPSC migration in response to SDF-1.

Conclusions:
Both CXCR4 and CXCR7 have distinct roles in the SDF-1/CXCR4/CXCR7 axis as network coordinators of cardiogenic induction and mobilization of hiPSCs. We contend that gaining further insight into the molecular nuances of this phenomenon will provide new insights for optimization of the cardiac repair potential of cell-based therapies.
Abstract 13301: Comparative Utilization of Cardiac Stress Testing in US Patients With and without Chronic Kidney Disease
Authors: Herzog Charles A , Natwick Tanya , Li Shuling , Charytan David M
Published: April 2024

Introduction:
A “nihilistic approach” to coronary artery disease (CAD) in pts with chronic kidney disease (CKD) has previously been reported. We have revisited this “truism” in the context of cardiac stress testing in the modern era (2008-12).

Methods:
The 20% Medicare sample was searched by single cohort years (2008-12) to identify pts age 65+ with no CKD (n = 4,232,080 in 2012) and Stages 1-5D CKD (n= 332,058 in 2012). Rates of non-invasive CAD testing (Stress: Echo, Nuclear, MRI, and ECG and CT: angiography or Calcium score) were estimated within each cohort by year.

Results:
Non-CKD demographics (2012): 33% age 75-84, 14% age 85+, 87% white, 7% black, 42% male; CKD (2012): 41% age 75-84, 25% age 85+, 81% white, 13% black, 47% male, 7% CKD stages 1 & 2, 64% 3,4,5ND, 7% ESRD, and 22% unknown stage.
Demographics of pts receiving tests
(2012):
non-CKD:
35% age 75-84, 6% age 85+, 88% white, 7% black, 48% male;
CKD:
44% age 75-84, 10% age 85+, 80% white, 13% black, 54% male, 7% CKD stages 1 & 2, 67% 3,4,5ND, 8% ESRD and 17% unknown stage. The rate of stress testing (per 100 pt-yrs) was 11.5 for non-CKD and 16.8 for CKD pts in 2008, declining to 9.4 and 13.4 respectively in 2012 (see figure for stress testing rate by yr). Stress nuclear testing predominated: 80.3% (non-CKD) and 88.2% (CKD) of all stress tests in 2008 and 77.7% (non-CKD) and 87.1% (CKD) in 2012 vs stress echo: 11.6% (non-CKD) and 7.4% (CKD) in 2008 and 12.6% (non-CKD) and 7.4% (CKD) in 2012. Approximately 2,000,000 Medicare pts age 65+ received a stress test In 2012.

Conclusions:
There has been a progressive decline in rates of stress testing in both non-CKD and CKD pts from 2008 to 2012. Stress nuclear imaging accounts for more than three-fourths of all stress tests. CKD pts have a consistently
higher
rate of stress testing compared to non-CKD pts in 2008-12. Commonly held perceptions of under-utilization of stress testing for CAD in CKD pts are false in the current era.
Abstract 13428: The Long-term Therapy With Low-dose Aspirin Did Not Reduce Cardiovascular Events in Patients With Type 2 Diabetes in Primary Prevention Setting: 10-year Follow-up of a Randomized Controlled Trial
Authors: Saito Yoshihiko , Okada Sadanori , Ogawa Hisao , Soejima Hirofumi , Sakuma Mio , Nakayama Masafumi , Dohi Naofumi , Jinnouchi Hideaki , Waki Masako , Morimoto Takeshi ,   the JPAD trial investigators
Published: April 2024

Introduction:
It takes long time to conclude efficacy and safety of an intervention on primary prevention of cardiovascular events. Up to date, there is no study to investigate the effect of the low-dose aspirin therapy on primary prevention of cardiovascular events in patients with diabetes with a follow-up period longer than 10 years.

Hypothesis:
The long-term therapy with low-dose aspirin prevents cardiovascular events in patients with diabetes and no pre-existing cardiovascular diseases.

Methods:
The Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes (JPAD) trial was a randomized controlled trial to examine whether the low-dose aspirin therapy reduces cardiovascular events in 2,539 Japanese patients with type 2 diabetes. The original JPAD trial reported that the low-dose aspirin therapy did not reduce cardiovascular events for a median of 4.4 years. After the JPAD trial was completed in 2008, we followed the patients until July 2015. In this period, the low-dose aspirin therapy was decided by each physician. We analyzed the effect of low-dose aspirin on incidence of cardiovascular events, according to the per-protocol principle.

Results:
The median follow-up period was 10.3 years, and 2,160 (85 %) patients remained the original allocation. The low-dose aspirin therapy did not reduce cardiovascular events based on the per-protocol cohort (HR, 1.14; 95% CI, 0.91 - 1.42; Figure). Cox proportional hazard models showed similar results (HR, 1.04; 95% CI, 0.83 - 1.30), adjusting age, sex, HbA1c, eGFR, history of smoking, and presence of hypertension and dyslipidemia. There were 54 (5%) hemorrhagic events in the aspirin group, and 72 (6%) in the no aspirin group (
P
= 0.5). Sensitivity analyses on the intention-to-treat cohort showed the similar results (HR, 1.01; 95% CI: 0.82 - 1.25).

Conclusions:
The low-dose aspirin therapy did not reduce cardiovascular events in patients with type 2 diabetes in primary prevention setting for 10-year follow-up.