bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 16798: MicroRNA 142-5p Targets Myocardial Hypertrophy and Cytokine Response
Authors: Sharma Salil , Liu Jing , Wei Jianqin , Bishopric Nanette H
Published: April 2024

Background:
p300 is a dose-dependent and limiting regulator of cardiac hypertrophy. p300 regulates hypertrophy by controlling the expression of specific microRNAs.

Objective:
To dissect the role of miR142 during hypertrophic growth and to verify its targets.

Methods and Results:
In mice with myocardial overexpression (OE) of p300 (p300tg) and in acute myocardial ischemia, we observed altered expression of microRNAs miR142-5p and -3p (miR142). Induction of myocyte hypertrophy in vitro and in vivo were associated with downregulation of miR142. Induction of miR142 by serum was sensitive to inhibitors of ERK/MAPK and JNK signaling pathways, establishing an inverse relationship between hypertrophic signaling and miR142 levels. Adenovirus-mediated OE of p300 in NRVM caused a steep reduction in miR142, while siRNA-mediated KD of p300 significantly upregulated miR142. Thus, p300 is both necessary and sufficient for miR142 downregulation. MiR142 altered the expression of many sarcomeric proteins including Tni2, Tnt2, Myh3 and Mlc1. MiR142 directly inhibited the translation of ACTN4 through a conserved 3’UTR binding site. MiR142 potently repressed multiple components of the NF-κB, TNF-α and interleukin signaling pathways and abrogated the upregulation of iNOS mRNA and NO production in myocytes exposed to cytokines. We identified IL6st/gp130 as a direct target of miR142 through paired 3’UTR 142-5p and -3p binding sites, implicating miR142 in myocyte survival signalling. Lentiviral transduction of miR142 confirmed the same gene targets in myocardium in vivo, associated with development of systolic dysfunction and extensive apoptosis at 2 months. Finally, miR142 inhibited the expression of p300 both in vitro and in vivo, through a miR142-5p 3’UTR binding site. Altered immune response gene expression in p300tg mice was restored to near-wt levels by miR142 OE, indicating that p300 and miR142 are mutually inhibitory.

Conclusion:
MiR142 is a potent inhibitor of myocardial cytokine signaling through repression of IL6st/gp130 expression. Induction of hypertrophy involves the MAPK-activated, p300-mediated inhibition of miR142, which removes a block to sarcomeric protein expression, gp130-mediated survival signaling, and sustained expression of p300.
Abstract 169: Neurological and Cardiovascular Outcomes After Cardiac Arrest at 6 Regional Interventional Cardiology Centers in the United States, 2007-2011
Authors: Seder David B , Mooney Michael , Patel Nainesh , McPherson John , McMullen Paul , Kern Karl B , Unger Barb , Browning J , Nanda S , Hacobian Melkon , Kelley M B , Nielsen Niklas
Published: April 2024

Background:
We characterized adverse events and outcomes among cardiac arrest (CA) survivors treated between 2007-2011 at six regional interventional cardiology (PCI) centers in the United States.

Methods:
Demographics, clinical features, adverse events, cardiovascular outcomes, and 6-month neurological outcomes of 663 sequential patients were retrospectively and prospectively entered into a secure, web-based registry (INTCAR). The overall survival of patients with VT/VF and PEA/asystole was calculated, and an expected “survival index” for each center developed

Results:
Patients were characterized as mean 61.3 (+14.9) years old, 69.2% male, 58.8% initial VT/VF, 23.5 (+16.3) minutes “downtime”. On admission, 31.1% had shock, 26% STEMI, 38.6% underwent urgent coronary angiography, and 20.2% urgent PCI. Moderate or severe left ventricular dysfunction was present in 63% patients on presentation and 49.5% at hospital discharge (P<0.001). Frequent adverse events were shock requiring vasopressors (81.6%) or balloon counterpulsation (9.5%), shivering requiring neuromuscular blockade (74.8%), hyperglycemia (66.1%), electrolyte disturbances (62.9%), arrhythmias (37.9%), seizures (26.5%), pneumonia (25%), and bleeding (9.5%). Of 370/663 (55.8%) patients that died during hospitalization, at a median of 4.7 (+3.9) days, discontinuation of life support occurred in 52%, and the cause of death was reported as neurological in 64.6% or cardiovascular in 35.4%. Good neurological outcome at 6 months was as follows: Overall (all rhythms) 38.2%, of VT/VF 53.2%, of PEA/Asystole 17.9 %, of those with shock on admission 38.1%. When corrected for case mix (%VT/VF vs. PEA/asystole), the ratio of actual to anticipated survival varied among centers from 0.87 to 1.43. Among patients surviving to discharge, 54.2% had reportedly normal left ventricular (LV) function, 29.2% moderate LV dysfunction, and 16.6% severe LV dysfunction. Of 282 patients surviving to 6-month follow-up, 89.7% were categorized as CPC1-2 and 10.3% as CPC 3-4.

Conclusions:
Across a geographically diverse group of PCI centers in the United States routinely employing therapeutic hypothermia for neuroprotection, cardiac arrest outcomes at centers employing TH and PCI were favorable.
Abstract 16912: The Incidence of the First Appropriate ICD Shock Remains Stable in Heart Failure Patients Over 6 Years
Authors: Singh Madhurmeet , Halder Indrani , Frangiskakis Michael , Grimley Sara , Gutmann Rebecca , McNamara Dennis , Schwartzman David , Saba Samir , London Barry
Published: April 2024

Introduction:
Implantable cardioverter defibrillators (ICDs) are indicated for primary and secondary sudden cardiac death (SCD) prevention in patients with systolic heart failure (HF). Most ICDs are never used; it is not known whether subjects who have never had an appropriate ICD shock after several years are at decreased SCD risk.

Method:
Data was collected on 384 subjects enrolled between March 2002 and November 2004 from one site of the Genetic Risk Assessment of Defibrillator Events (GRADE) study, a prospective observational study of subjects with severe systolic dysfunction (EF < 30%) and ICDs. The incidence of the first appropriate ICD shock for VT or VF and of death/transplant/VAD (DTV) was calculated for years 1 to 6.

Results:
The cohort was 62±12 yrs old, 78% male, 95% white, 76% ischemic, EF 20±6 %, NYHA class 2.3±0.6, median f/u 43 months. 110 (29%) subjects reached the primary endpoint of appropriate ICD shock, and 186 (48%) reached the combined endpoint of DTV. The incidence of the first appropriate ICD shock was highest in year 1 (12.8%) but remained high through year 6 (6.8%; Figure). Similarly, the rate of DTV remained ~10% per year. Of note, 50% of subjects reached the combined endpoint of DTV within 1 year after their first appropriate shock.

Conclusion:
The absence of an early appropriate ICD shock does not predict the absence of future shocks in HF patients. This likely reflects the progressive nature of HF in this cohort. Thus, ongoing generator changes should be recommended for subjects with low EFs, even in the absence of early appropriate shocks, as these patients remain at a substantial risk for SCD.
Abstract 16934: UC1002, a Carboxyl Ester Lipase Inhibitor, Raises HDL in CETP Transgenic Mice and Increases Reverse Cholesterol Transport, and Also Lowers LDL and VLDL in Mice Fed Western Diet
Authors: Howles Philip , Bailey Laura , Jones Jennifer , Thornicroft Jennifer , Hu Eric , Wang Jiang , Hui David Y
Published: April 2024

Background:
Raising HDL and increasing reverse cholesterol transport (RCT) are believed to lower cardiovascular risk independently of decreasing LDL. We recently documented increased RCT in carboxyl ester lipase (CEL) knockout mice by a mechanism that involves both increased biliary transport of HDL cholesteryl ester and lack of cholesteryl ester hydrolysis in intestine. We have also shown that lack of CEL in mice expressing CETP raises serum HDL due to increased hepatic production. Objective: To test the efficacy of CEL inhibitor, UC1002, with respect to increasing RCT and raising HDL in CETP transgenic mice; to test the efficacy of UC1002 in reversing hyperlipidemia in Western diet-fed CETP transgenic mice.

Methods:
Wild type C57BL/6 mice or C57BL/6 mice with a CETP transgene were given UC1002 daily for 2 weeks in chow at doses of 50-150 mg/kg b.w. (n = 6-12). Sterol excretion was measured before and after treatment or was measured in control groups fed normal chow. HDL was measured by heparin/Mn precipitation or by FPLC fractionation. A cohort of CETP transgenic mice heterozygous for LDL receptor deletion was fed Western diet for 16 weeks followed by 6 weeks of diet with UC1002+simvastatin, statin alone, or no drug treatment (6 per group). At the end of the test period, serum lipids, lipoproteins, and liver enzymes were quantified, and tissues harvested.

Results:
Maximum efficacy was achieved at 100 mg/kg of UC1002, which increased fecal sterol excretion by 60% (P = 0.005), and, In CETP mice, raised HDL by 26% (44.4 ± 6.5% to 56.0 ± 3.2% of plasma cholesterol, P = 0.005). In Western diet fed CETP/LDLR+/− mice, UC1002+statin reduced triglycerides 54% (P < 0.001), reduced LDL 26% (P = 0.002), and raised HDL 14% (P = 0.003) compared to statin alone. Serum ALT was reduced 67% (P = 0.016) by the combined treatment compared to no treatment. Liver histology indicated ∼50% less necrosis and macrosteatosis with both treatment regimens. No pathology was associated with UC1002.

Conclusions:
CEL inhibitor UC1002 improves reverse cholesterol transport and serum lipoprotein profiles in CETP mice with diet-induced dyslipidemia similar to that in humans. Thus, targeted CEL inhibition may be a novel strategy for treatment of hyperlipidemia to decrease the risk of cardiovascular disease.
Abstract 16939: Scar/EF Assessed by Delayed Hyperenhancement Cardiac MRI is a Novel Viability Index Which Independently Predicts Survival in Patients with Severe Ischemic Cardiomyopathy
Authors: Kwon Deborah H , Hachamovitch Rory , Popovic Zoran B , Starling Randall C , Desai Milind Y , Flamm Scott D , Marwick Thomas
Published: April 2024

Introduction:
Myocardial scar burden (MSB) is an independent predictor of mortality in ischemic cardiomyopathy (ICM). However, the integration of MSB with resultant EF has not previously been assessed as a predictor of outcomes in severe ischemic cardiomyopathy.

Purpose:
We sought to compare the association of scar/EF and other traditional viability indexes with outcomes in severe ICM.

Methods:
335 patients with > 70% stenosis in ≥1 epicardial coronary artery (75% men, median age 64 years, median LV ejection fraction (EF) 22 %, median ESVi 109cc) underwent delayed hyperenhancement(DHE)-MRI between 2003-2007. Scar was defined as > 2 SD above normal myocardium. . LV scar score (summed segmental scar score per patient divided by 17) was recorded as: 0 = none, 1 = 1-25%, 2 = 26-50%, 3 = 51-75%, and 4 = > 75%. LV volumes and LV ejection fraction were calculated Scar/EF was defined as scar score/EF. Cox proportional hazards survival modeling of a composite end-point (CE; cardiac transplantation, all-cause mortality) was used to risk-adjust comparisons.

Results:
Over a follow-up of up to 8 years[mean 5.5 years], 131 events occurred (126 deaths, 5 cardiac transplantations). Revascularization within 90 days after testing (REV) occurred in 168 patients and was modeled with logistic regression to develop a propensity score. Survival analysis revealed that after adjusting for prior CABG/PCI, sex, diabetes, age, use of CRT, ICD, mitral valve or aortic valve procedures, scar/EF(

χ
2

18.4, Global

χ
2

53), scar score(

χ
2

9, Global

χ
2

44.9), EF(

χ
2

4.5, Global

χ
2

40), ESVi (

χ
2

4.5, Global

χ
2

40) were predictors of CE. However, scar/EF was the most powerful, independent predictor of CE in the global model. For each of these models, only the addition of scar/EF further increased the

χ
2

power
.

Conclusions:
Scar/EF assessed by DHE-MRI is a novel powerful incremental prognostic viability index in patients with severe ICM and has superior prognostic power compared to traditional viability indexes.
Abstract 17087: Doubled Survival From Out-of-Hospital Cardiac Arrest in a Rural Community in North-Norway Following Implementation of an Aggressive Chest Pain Protocol with Early Prehospital Thrombolysis for STEMI
Authors: Lien Nilsen Janne M , Bø Ida , Rasmussen Jan R , Haanaes Esten K , Gilbert Mads
Published: April 2024

Introduction
Survival from prehospital cardiac arrest (PCA) remains low. Tromsø municipality in rural North-Norway has a mixed urban-rural population of 60.000, good ground and air ambulance systems, short response times, and dispatch centres staffed with nurses and paramedics, all loyal to current guidelines.

Hypothesis
By changing focus from the onset of ‘
collapse
’ in PCA to the onset of
chest pain
in acute coronary syndrome, we hypothesized that more PCA-patients could survive by saving time to alarm, dispatch, diagnosis and first defibrillation. We started an aggressive criteria based prehospital chest pain protocol in 2000. Local GPs and ambulance paramedics were trained in symptoms and signs of STEMI, to access and transmit prehospital 12-leads ECG, give MONA as well as early prehospital thrombolysis (PHT) to patients with prehospital diagnosed acute STEMI. We applied defibrillation pads to all chest pain. The population was informed through media stunts.

Methods
Retrospective study of survival from PCA during two 5-years periods in Tromsø (1999 -2004; 2004-2009). Each PCA patient's Utstein-chart, digital dispatch centre logs, hospital records and non-survivors autopsy reports were analysed.

Results
Annual incidence of PCA with resuscitation attempts and ambulance dispatched was 45,3 pr. 100.000. During first 5-years, 10,5 % of all patients (18/172) with PCA were discharged alive. During second period, survival to discharge doubled to 22,3 % (31/139, p<0,05). Presence of an initial shockable rhythm (VF/VT) increased significantly. In patients with witnessed PCA of cardial etiology and a shockable first rhythm, survival to discharge was 21,4 % during the first 5-years period, but doubled to 44,2 % (19/43, p<0,05) in the second period. CPR was started by lay bystanders prior to ambulance arrival in 68,2 % of patients during first, increasing to 76,3 % during the second study period (NS). Prehospital ambulance response time was unchanged at 10 min in each period. By moving system attention ‘to the left of cardiac arrest’, survival to discharge doubled.
Abstract 17185: Diastolic Dysfunction is a Risk Factor for Mortality in Patients Undergoing Liver Transplantation
Authors: Cordero-Reyes Andrea M , Estep Jerry D , Torre-Amione Gulliermo , Orrego Carlos M
Published: April 2024

Introduction.
Cardiac dysfunction in cirrhotic patients is a compilation of manifestations that lead to a hyperdynamic state. The influence of the cardiovascular system and its derangements in these patients has been described but its influence on prognosis and outcome is not well defined.

Methods.
A retrospective review of 348 patients that underwent liver transplantation at The Methodist Hospital from 2004-2010 was performed under an approved IRB protocol. Charts were obtained from the liver transplant database and information collected regarding cardiovascular profile previous to transplant. Logistic regression adjusted for confounders was performed and statistical significance is defined as p < 0.05.

Results.
Patient demographics are described in table 1. 65% of the patients were male and 35% female. 65% were also Caucasian, 18% Hispanic and 10% African-American. There were several cardiovascular manifestations in this patient population such as prolonged QTc in 32%, rhythm abnormalities (predominantly heart block) in 9% of patients, pulmonary AV fistula in 18%, PFO in 9% and diastolic dysfunction was present in 22% of patients. When adjusting for possible confounders, Diastolic Dysfunction, independent of filling pressures, was the only predictor of mortality with a p <0.05 with an Odds Ratio and Confidence Interval of 2.3, 2.0-3.2 respectively.

Conclusions.
In conclusion, Diastolic Dysfunction is a risk factor that needs to be considered when evaluating and managing cirrhotic patients that will undergo liver transplantation in order to reduce morbidity and mortality.
Abstract 17217: Impaired Coupling of Myocardial Blood Flow to Cardiac Work Leads to Cardiac Dysfunction
Authors: Ohanyan Vahagn A , Yin Liya , Pung Yuh F , Enrick Molly , Hakobyan Tatevik A , Kolz Christopher L , Logan Suzanna , Bratz Ian , Chilian William M
Published: April 2024

The heart is highly dependent on a continuous supply of oxygen from the coronary circulation to meet its metabolic requirements. There are many mechanisms that contribute to the regulation of coronary blood flow, including redox and oxygen sensing voltage-gated potassium channels. These channels are expressed in coronary smooth muscle cells and appear to couple cardiac work to myocardial blood flow; specifically, we found reduced levels of flow per unit of cardiac work in mice null for the redox sensing Kv1.5 channel (Kv1.5
-/-
) compared to wild types (WT). Accordingly, we hypothesized that Kv1.5
-/-
mice, with impaired coronary metabolic dilation, would gradually develop cardiac pump dysfunction due to inadequate perfusion which would lead to microareas of hypoxia, then to apoptosis, to diffuse fibrosis and finally cardiac dysfunction.

Methods:
Kv1.5
-/-
male mice (n=8) and WT (n=6) were used for this study. For cardiac function measurements, transthoracic echocardiography was performed under sevoflurane anesthesia at 4, 8 and 12 months. After echocardiography, animals recovered and measurements were repeated at 8 and 12 months of age. As shown in the diagram, at 4 months of age, %EF is 13% lower in Kv 1.5
-/-
mice compared to WT animals (P<0.05). In Kv 1.5
-/-
mice at 8 and 12 months, %EF was 20% and 23% lower, respectively, compared to WT animals (P<0.05). Although the E/A ratio, a measure of diastolic function, did not show a significant decline in the Kv1.5
-/-
mice compared to WT, there was a trend towards diastolic dysfunction. Hypoxyprobe staining (to label protein adducts produced by severe hypoxia) revealed microareas of hypoxia in hearts from the Kv1.5
-/-
mice, but no such areas in WT. Also, Kv1.5
-/-
mice show much more collagen deposition in the myocardium than WT. Based on these data, we conclude that alteration in the coupling of myocardial blood flow to cardiac work can lead to cardiac systolic and diastolic dysfunction
Abstract 17270: The Effects of Cardiac Resynchronization Therapy on Myofilament Calcium Sensitivity are Global and Mediated by Protein Phosphorylation
Authors: Kirk Jonathan A , Tunin Richard S , Gao Weidong , Kass David A
Published: April 2024

We have previously shown that calcium sensitivity is significantly decreased with dyssynchrony, but is improved with cardiac resynchronization therapy (CRT) using trabeculae from the right ventricle (RV). However, dyssynchrony and resynchronization cause regional changes in stress, with the RV and left ventricle (LV) experiencing differing loads. To investigate the regional effects of CRT, we used 3 canine models: dyssynchronous heart failure (HF
dys
, left bundle ablation, 6 wks atrial tachypacing), CRT (left bundle ablation, 3 wks atrial tachypacing, 3 wks biventricular tachypacing), and non-paced controls. Steady-state force-calcium relationships were measured in skinned myocytes isolated from the LV lateral wall. Compared to control, HF
dys
exhibited decreased maximal calcium-activated force (F
max
, Con: 35.00 ± 4.61 93 mN•mm
-2
, n = 7 myocytes from 3 dogs, HF
dys
: 13.44 ± 1.66 mN•mm
-2
, n = 7 myocytes from 3 dogs,
P
< 0.01), and decreased calcium sensitivity (EC
50
, Con: 1.92 ± 0.16 μM, HF
dys
: 2.58 ± 0.11,
P
< 0.01). These parameters were returned to near control values in the CRT dog (F
max
: 36.16 ± 2.78 mN•mm
-2
, EC
50
: 2.00 ± 0.19 μM, n = 8 myocytes
P
< 0.05 vs HF
dys
,
P
= N.S. vs Con). To discover if these changes were mediated by altered phosphorylation state, we treated skinned RV trabeculae muscles with the phosphatase PP1 (2,500 U/ml) for 60 minutes, and measured force-calcium curves before and after treatment. None of the groups had a statistically significant change in F
max
after treatment (
P
= N.S.). However, there was an increase in EC
50
in both Con (ΔEC
50
: 1.09 ± 0.22 μM,
n
= 6) and CRT (ΔEC
50
: 0.70 ± 0.23 μM,
n
= 5), while there was no effect on HF
dys
trabeculae (ΔEC
50
: -0.06 ± 0.14 μM,
n
= 5,
P
< 0.05 vs Con and CRT). This suggests that myofilament protein phosphorylation is responsible for the changes in calcium sensitivity. In summary, these results show that despite opposing regional changes in stress, the myofilament responds in a globally homogenous manner and is mediated by altered global kinase/phosphatase activity, and not by local stress response. Overall, this is encouraging data for the development of a pharmacological intervention to recreate the beneficial aspects of CRT, since regional targeting may be unnecessary.
Abstract 17370: Perceptions of Patients with Stable Coronary Disease and Adherence to Dual Antiplatelet Therapy 30-Days after Coronary Angiography
Authors: Fennessy Michelle M , Ryan Catherine , DeVon Holli , Nguyen Bryant H , Lopez John J , Zerwic Julie
Published: April 2024

Background
:

Platelet inhibition is an important focus of medical management in patients with stable coronary artery disease (CAD), with multiple patient-related factors linked to dual antiplatelet therapy (DAPT) non-adherence. However, little is known about illness perceptions surrounding the use of antiplatelet medications and whether they differ in patients who are treated with medical and/or interventional approaches. The purpose of this study was to compare differences in illness perceptions of patients with stable CAD and report adherence to DAPT 30 days after initiating treatment.

Methods
:

Subjects (
n
=180) were recruited after coronary angiography and optimal medical therapy (OMT) (
n
=90) and percutaneous coronary intervention and optimal medical therapy (PCI/OMT) (
n
=90). The Illness Perception Questionnaire-Revised (IPQ-R) was administered at baseline and 30-days after treatment, with a response rate of 52.8% (
n
=95) at 30-days. Patients were predominantly male (71.7%) with a mean age of 65.1 (±8.3). Adherence to DAPT (aspirin and thienopyridine) at 30-days was collected using a health history update.

Results
:

Adherence data (mean ± SEM) and IPQ-R subscale Timeline scores are shown
.
Adherent PCI/OMT subjects had significantly higher acute/chronic timeline (aspirin:
t
=-3.5,
p
=.01; thienopyridine:
t
=-4.3,
p
=<.001) and timeline cyclical scores (aspirin
t
=-2.5,
p
=.01; thienopyridine:
t
=-2.8,
p
=.009).

Conclusions
:

Overall, patients who perceived their illness to be chronic instead of acute were more likely to remain adherent to their antiplatelet medications 30 days after treatment. Higher timeline cyclical scores were reported in patients who were adherent to antiplatelet medications after PCI/OMT, which suggests the influence of continued symptoms as an indicator for adherence. A tailored educational approach regarding dual-antiplatelet medications may be needed to reinforce long-term therapy in this population of patients.
Abstract 17398: Prediction of Improvement in Cardiac Function by Dobutamine Echocardiography in Patients with Recent Onset Dilated Cardiomyopathy
Authors: Yang Dong Heon , Lee Ju Hwan , Kim Kyun Hee , Park Sun Hee
Published: April 2024

Background:
Clinical and echocardiographic variables have been used to predict prognosis in patients with DCM. The aim of this study was to investigate whether the contractile reserve on dobutamine stress echocardiography (DSE) could predict the myocardial contractile reversibility or prognosis in patients with recent-onset DCM.

Method:
High-dose DSE was performed in 22 patients with recently diagnosed DCM in incremental stages lasting 5 min each. Left ventricular (LV) volume and ejection fraction (EF) was measured by Simpson's biplane method. LV end-systolic elastance (Ees), effective arterial elastance (Ea) and ventriculo-vascular coupling index (VVID) were also calculated. A follow-up echocardiography was done at 9±6 months.

Results:
Fourteen patients were men and age was 46±16 years. Resting LVEF, LV end-diastolic volume and LV end-systolic volume was 24±6%, 174±53 mL and 133±44 mL. LVEF were increased to 31±9% at low dose dobutamine and to 36±9% at peak dose dobutamine stimulation. Follow-up LVEF was 39±15% after 9±6 months . Resting LVEF, LV volume, stroke volume, E/E', Ees, Ea and VVID could not predict follow-up LVEF. However, LVEF, LV volumes, Ees and VVID at peak dose on high-dose DSE, not at low dose, was well correlated with follow-up LVEF, especially peak LVEF was most strongly correlated (Fig 1). During follow-up period, 3 died of cardiac causes and 5 readmitted for aggravation of heart failure. In patients with cardiac events, LVEF was lower, LV volumes were higher and changes of LVEF from resting to peak dobutamine were lower. The addition of high-dose DSE resulted in significant incremental improvement in the predictive value of the other parameters (Fig 2).

Conclusion:
High-dose DSE could predict late spontaneous improvement in cardiac function in patients with recent-onset DCM and had prognostic values for future cardiac events.
Abstract 17614: Genome-Wide Association Study of Aspirin Responsiveness in African Americans
Authors: Qayyum Rehan , Becker Diane M , Yanek Lisa R , Faraday Nauder , Suktitipat Bhoom , Mathias Rasika , Becker Lewis C
Published: April 2024

While familial studies have established that inter-individual variability in platelet response to aspirin (ASA) is partly due to genetic variation, a genome-wide association study (GWAS) has not been reported in African Americans. Fasting blood samples were obtained from healthy African Americans (N=868) with family history of premature coronary artery disease. Optical aggregation was measured in platelet-rich plasma (PRP) after samples were stimulated with collagen (1, 2, 5 µg/mL), ADP (2, 10 µmol/L), or epinephrine (2, 10 µmol/L) before and after 14-days of ASA therapy. A cohort of European ancestry (N=1236) provided replication. In each cohort, age- and sex-adjusted linear mixed effects models adjusting for family structure were used to test for association between each SNP and each phenotype under an additive model. We analyzed data with adjustment for pre-ASA platelet studies to examine the pure effect of ASA and without adjustment which is likely to be closer to the clinically observed effect. We sought region-based replication with adjustment for the number of LD blocks in HapMap CEU population. We observed SNPs in 3 regions (2 intronic and 1 intergenic) that crossed GWAS threshold of significance (p<5 x 10
-8
). A SNP in the
PEAR1
gene, rs12041331, was significantly associated with most doses of the three agonists and this association remained significant after adjusting for pre-ASA platelet studies (Table). In the replication cohort, rs12041331 was also nominally significant. SNPs close to the other two GWAS-significant SNPs were nominally significant in the replication cohort after adjusting for the LD structure. In this first GWAS of platelet response to ASA therapy in African Americans, we show a relationship between post-ASA platelet reactivity and 3 regions, and replicate these findings in an independent sample. Both
PEAR1
and
CRB1
are expressed in platelets and are good candidates for follow-up studies examining ASA responsiveness.
Abstract 17738: CRP Predicting Locus at 6q22 Modulates Risk of Ventricular Fibrillation in Acute Myocardial Infarction
Authors: Pazoki Raha , Tanck Michael W , Dalal Darshan , de Jong Jonas S , Wilde Arthur A , Bezzina Connie R
Published: April 2024

Sudden cardiac death is a leading mode of death in adults in the Western world and is largely caused by ventricular fibrillation (VF) during acute myocardial ischemia-infarction (MI). A genetic component in risk of VF in the setting of MI is recognized. However, the underlying genetic factors remain largely unknown. Plasma concentration of C-reactive protein (CRP) is a predictor of sudden cardiac death. Recently, several single nucleotide polymorphisms (SNPs) have been revealed to be associated with CRP levels in genome-wide association studies (GWAS). In this study we investigated the effect of CRP-predicting SNPs in modulation of risk of VF in acute MI.

Methods:
Patients studied were from the Arrhythmia Genetics in the NEtherlands Study (AGNES), consisting of patients with a first acute MI, with those suffering VF classified as cases (n=515) and those not suffering VF classified as controls (n=457). Twenty independent SNPs (r2<0.75) previously found to be associated with CRP levels at genome-wide significant p-values (P<5e-08) in previous GWAS were identified. Genotypes were obtained by direct genotyping (Illumina 610) or were imputed using HapMap. A Bonferroni-corrected threshold of P<0.002 was used to define statistical significance in testing of individual SNPs. We also generated a genetic risk score based on the number of CRP-increasing alleles. Logistic regression modeling was used to test for association with VF.

Results:
SNP rs6901250 in GPRC6A was strongly associated with VF in acute MI (OR:1.39;95%CI:1.14,1.69;P=9.6e-04), with the CRP-increasing allele being associated with increased risk for VF. Analysis of SNPs in a 50 Kb region around rs6901250 identified a stronger signal at SNP
rs633420
(P=9.7e-05) which was in high linkage disequilibrium (r2=0.73) with rs6901250. The CRP genetic risk score generated based on the number of CRP-increasing alleles was associated with risk of VF after MI (OR: 1.07; 95%CI: 1.01,1.12; P=0.01).

Conclusions:
CRP-predicting loci in aggregate and rs6901250 individually are associated with risk of VF in MI. Our study highlights the role of inflammatory loci on risk of VF after acute MI.
Abstract 17781: Relationship Between Epicardial Adipose Tissue and Coronary Arterial Remodeling as Assessed by Intravascular Ultrasound in Patients with Coronary Artery Disease
Authors: Ogura Riyo , Hiasa Yoshikazu , Takahashi Takefumi , Hosokawa Shinobu , Kishi Koichi , Ohtani Ryuji
Published: April 2024

Background:
Recently, the interest in epicardial adipose tissue (EAT) is rapidly growing. Several study suggest that EAT induces inflammation of the artery wall by secretion of pro-inflammatory proteins and plays a role in the pathogenesis of coronary artery disease. However, there is no information regarding the impact of EAT on coronary arterial remodeling and plaque vulnerability.

Objectives:
The aim of this study was to evaluate the relationship between EAT and intravascular ultrasound (IVUS) findings, mainly remodeling, in patients with coronary artery disease.

Methods:
One hundred and eight consecutive patients with de novo lesions located in native coronary artery were studied. The EAT thickness on the right ventricle was measured using transthoracic echocardiography, and arterial remodeling of culprit lesion was assessed by preinterventional IVUS. The remodeling index (RI) was calculated as lesion divided by the reference external elastic membrane cross-sectional area, Positive remodeling (PR) was defined as RI>1.05, intermediate remodeling (IR) as between 0.95 and 1.05, and negative remodeling (NR) as <0.95. IVUS findings included plaque characteristics-lipid rich, mixed and calcified plaque and plaque eccentricity.

Results:
There was significant relationship between EAT thickness and RI(r= 0.36, p=0.0001). Higher EAT thickness (≥10mm, n=55) were associated with higher BMI(25.2±3.6 kg/m
2
vs. 23.9±2.8 kg/m
2
, p=0.04), plasma triglyceride level (189.1±103.8 mg/dl vs. 146.1±80.9 mg/dl, p=0.02), and plasma urinary acid level(6.8±1.5mg/dl vs. 5.9±1.5 mg/dl, p=0.02). PR and more lipid rich and mixed plaque were observed in patients with higher EAT thickness than lower EAT thickness (PR ;43.6% vs. 18.9%,p=0.02. lipid rich and mixed plaque; 89% vs.66%,p=0.004). Multivariate analysis showed high EAT thickness was independent factor affecting coronary positive remodeling (OR3.05,p=0.02).There was no significant association EAT thickness and plaque eccentricity.

Conclusion;
High EAT thickness was significantly correlated with the coronary positive remodeling and non calcified plaque characteristics.
Abstract 17786: Presence of an Esophageal Temperature Probe During Pulmonary Vein Isolation: Is There an Increased Risk for Esophageal Lesion Development?
Authors: Fuernkranz Alexander , Metzner Andreas , Tilz Roland , Mathew Shibu , Wissner Erik , Rillig Andreas , Ouyang Feifan , Kuck Karl-Heinz
Published: April 2024

Background:
Luminal esophageal temperature (LET) measurement is investigated as a tool to decrease risk of esophageal lesion formation during pulmonary vein isolation using radiofrequency (RF) current. However, recent evidence from duty-cycled phased RF ablation revealed a possible contributing role of the esophageal probe to lesion formation by direct tissue heating or interaction with the ablation device. Whether the presence of a LET probe may increase lesion formation during conventional irrigated RF ablation has not yet been investigated.

Methods and Results:
62 patients (65% male, age 63±11 years, LA 44±10 mm) with drug-resistant atrial fibrillation underwent circumferential pulmonary vein isolation (PVI) using irrigated RF energy and a 3D-mapping system. A maximum power of 30 Watts was applied at the left atrial posterior wall (LAPW). In 30 patients a LET probe with 5 metal electrodes (3 thermistors) was placed in the esophagus and continuously adjusted to the level of the target pulmonary vein (group 1). LET measurement was observational only and no temperature cutoff was used. In the remaining 32 patients, no LET probe was placed (group 2). All patients underwent gastro-esophagoscopy 2±1 days after the procedure. The cumulative RF energy applied to the LAPW was 21368±9449 Joules (group 1) and 18092±8143 Joules (group 2, p=0,15). Esophageal lesions were found in 12 patients (40%) of group 1 (ulcerations: 4, erythema: 8), and 11 patients (34%) of group 2 (ulcerations: 5, erythema: 4); p=0,65. Lesions healed without clinical sequelae on proton pump inhibitor therapy in all patients. Within group 1, maximum LET in patients with and without lesions was 45,7±3,7 °C and 43,8±3,9 °C, respectively (p=0,20).

Conclusion:
The incidence of reversible esophageal lesions after circumferential PVI using irrigated RF energy was similar whether or not a temperature probe was present in the esophagus when no temperature cutoff was used.
Abstract 17819: Predicting the Proportional Risk of Sudden Cardiac Death in a Multicenter Heart Failure Cohort
Authors: Shadman Ramin , Poole Jeanne E , Mozaffarian Dariush , Cleland John G , Swedberg Karl , Maggioni Aldo P , Anand Inder S , Carson Peter , Levy Wayne
Published: April 2024

Introduction:
Many patients with heart failure die suddenly. Implantable
cardiac
defibrillators (ICDs) can reduce the rate of sudden death. Strategies that help identify patients who have most to gain from an ICD could reduce morbidity and maximize cost-effectiveness of ICDs.

Methods:
We used data from 9,885 heart failure patients, of whom 2,549 died during an average follow-up of 2.3 years. Using commonly available baseline clinical and demographic information, we developed a mode-specific multinomial logistic regression model to identify variables associated with a disproportionate fraction of total mortality due to sudden death.

Results:
In multivariable-adjusted models, we confirmed that commonly utilized variables for ICD implantation decisions, such as lower ejection fraction (OR for sudden death vs. other deaths: 1.15 per 10% decrease, p=0.005) and better New York Heart Association functional class (OR 1.30 for class 2 versus 3/4, p=0.004) were associated with greater proportion of deaths due to sudden death. We also demonstrated that younger age (OR 1.25 per decade younger, p<0.001), male sex (OR 1.40, p=0.002), and higher body mass index (BMI) (OR 1.24 per 5 kg/m
2
, p<0.001) independently increased the chance that if a patient died, it would be due to sudden death. Patients with diabetes (OR 0.75, p=0.001), systolic BP deviating above or below 140mmHg (OR 0.92 per 10mmHg, p=0.005), higher creatinine (OR 0.65 per mg/dL, p<0.001), or lower serum sodium (OR 0.96 per mEq below 138, p=0.029) had a lower proportional risk of sudden death. The use of several heart failure medications, left ventricular end-diastolic dimension, or plasma NT-proBNP levels was not independently associated with risk of sudden versus non-sudden death.

Conclusions:
Several demographic and clinical variables beyond ejection fraction and functional class are independently associated with higher or lower proportional risk for sudden death. Our findings support the need for further investigation whether this novel predictive model, in the context of absolute mortality rates, can be used to target the use of ICDs and other life-saving therapies to populations who will derive greatest benefit from their application.
Abstract 17863: Renal Function and Coronary Artery Disease Progression in Patients with Acute Coronary Syndrome
Authors: Nakachi Tatsuya , Fukui Kazuki , Nakagawa Takeshi , Ohkusu Yasuo , Muto Kazuhiro , Kato Shingo , Kusakawa Yuka , Ishii Nao , Kosuge Masami , Kimura Kazuo
Published: April 2024

Background:
Renal dysfunction is a powerful predictor of adverse outcomes in acute coronary syndrome (ACS); however, its underlying mechanism has not been fully elucidated. Although renal dysfunction has been shown to be associated with the severity of coronary artery disease (CAD), the relation between renal function and CAD progression remains unclear.

Methods:
We studied 209 patients with ACS who underwent percutaneous coronary intervention (PCI) for culprit lesion during initial hospitalization. All patients underwent serial coronary angiograms (CAGs) immediately before PCI, and at 8 + 3 months and 60 + 10 months after presentation. Coronary disease progression (CP) was defined as an increase > 15 % in stenosis severity of lesion in nonculprit artery between 2 serial CAGs. Estimated glomerular filtration rate (eGFR), cardiac-specific troponin T and lipid profiles were measured on initial admission. Patients were divided into tertiles according to eGFR at initial admission: the lower [T1; eGFR 54 + 9 mL/min/1.73m
2
, n=70], the middle [T2; eGFR 71 + 6 mL/min/1.73m
2
, n=69], and the upper tertile [T3; eGFR 102 + 20 mL/min/1.73m
2
, n=70].

Results:
There were no differences in gender, coronary risk factors, lipid profiles, positive-troponin T, follow-up periods and medications in the 3 groups. In T1,T2, and T3, ages were 68 + 7, 63 + 10, and 60 + 11 years (p<0.001). The rate of multivessel disease were 71, 55, and 51 % (p=0.047). The rate of CP between first and second CAGs was highest in T1 (41%), followed by T2 (24%), and lowest in T3 (21%) (p=0.046). The rate of CP between second and final CAGs was highest in T1 (49%, 31%, and 30% in T1, T2, and T3, respectively; p=0.033). Multivariate analysis revealed that T1 (OR 2.82, 95% CI 1.12 to 6.64, p=0.018) and age > 65 years (OR 2.68, 95% CI 1.08 to 6.64, p=0.033) were independently associated with the presence of both of CP between each of 2 serial CAGs.

Conclusions:
In patients with ACS, renal function is associated with not only the severity of CAD but also continuous CAD progression. These findings may partly explain adverse outcomes in patients with renal dysfunction.
Abstract 179: Cerebral Performance Category and Long-Term Prognosis in Cardiac Arrest Survivors
Authors: Phelps Randi J , Rea Thomas , Maynard Charles , Dumas Florence
Published: April 2024

Background:
Cerebral Performance Category (CPC) is commonly used to assess neurologic outcome among cardiac arrest survivors. However the prognostic ability of the CPC is uncertain. We evaluated the association between CPC and long-term survival among persons resuscitated from out-of-hospital cardiac arrest.

Methods:
We conducted a cohort investigation of all persons > 18 years suffering out-of-hospital cardiac arrest in a large metropolitan EMS system between January 1, 2001 and December 31, 2009 who were resuscitated and discharged alive from the hospital. CPC was determined by review of hospital records to assess neurological status at discharge. Long-term vital status was ascertained using the state death certificate listing and the National Social Security Death Index through December 31, 2010. Kaplan-Meier was used to evaluate the association between CPC and survival.

Results:
During the study period 1001 adults were discharged alive following resuscitation, 980 with available CPC score. At hospital discharge, 62% had CPC of 1, 23% had CPC 2, 10% had CPC 3, and 5% had CPC 4. Average follow up was 4.8 years (SD=2.6). Overall 5-year survival was 65%. CPC was strongly associated with long-term survival, shown in Figure 1. Five year survival was 75% for CPC 1, 56% CPC 2, 48% CPC 3, and 23% for CPC 4 (log rank, p <0.0001).

Conclusion:
Neurological status at hospital discharge as measured by the CPC predicts long-term prognosis following resuscitation from out-of-hospital cardiac arrest. The findings support efforts designed to improve neurological recovery to achieve better long-term prognosis.
Abstract 17909: Ventricular Fibrillation During First 48 Hours of ST-Elevation Myocardial Infarction Treated with Primary Angioplasty Increases In-Hospital Mortality but Does Not Affect One-Year Survival in Patients Discharged Alive
Authors: Demidova Marina M , Höijer Carl-Johan , Erlinge David , Platonov Pyotr G
Published: April 2024

Background:
ICD implantation is not advocated for survivors of ventricular fibrillation (VF) during first 48h of ST-elevation myocardial infarction (STEMI). However the guidelines are based mostly on the data obtained before primary percutaneous coronary interventions (PCI) had become a standard of care. Long-term follow-up studies in contemporary real-life STEMI population are lacking. Our aim was to assess the prognostic value of early VF in non-selected population of PCI-treated STEMI patients.

Methods:
Consecutive patients admitted to a tertiary care hospital for primary PCI during 2007-2009 were identified using hospital registry (n=1740, age 66±12 years, 71% male). The registry data were used to find those who had VF documented during index admission and their medical records were scrutinized for VF timing in regard to the symptom onset. Information regarding ICD implants during follow-up was retrieved from the ICD registry and delivery of adequate ICD therapy was checked in medical records. Kaplan-Mayer analysis was performed on patients alive at 48 hours after symptom onset using death at 1 year as a primary endpoint. Death, resuscitated VF or adequate ICD therapy was used as a combined endpoint.

Results:
Early VF occurred in 7% of STEMI patients (n=124, age 67±12, 73% male, VF group). In patients alive at 48h (n=1684), VF patients (n=103) had higher in-hospital mortality (12% vs 2%, p<0,001, Figure). During follow-up, 22 patients received ICD for primary and 4 for secondary prevention (two of the later had adequate ICD-therapy). In those discharged alive (n=1646), VF patients (n=91) had low mortality (1%) and combined endpoint rate (3%) that did not differ compared to NoVF patients (4% and 4% respectively).

Conclusion:
In a large non-selected population of STEMI patients treated by primary PCI, VF during the first 48h of STEMI is associated with increased in-hospital mortality but does not influence the long-term prognosis for those discharged alive
Abstract 18006: A Simple Novel SELF-Pathway Appropriately Identify High Risk Patients When Admitted with Unexplained Syncope
Authors: Aziz Emad F , Pamidimukala Chaithanya K , Pratap Balaji , Bastawrose Joseph H , Park Terrence , Lee Steven , Javed Fahad , Herzog Eyal
Published: April 2024

Background:
We developed a novel SELF pathway to guide physicians in risk stratification of patients with unexplained syncope. According to our pathway patients are risk stratified twice using the acronyms SELF-A (Short period, Early-rapid onset, Loss of consciousness, Full recovery) and SELF-B (Structural heart disease, abnormal Ecg, and arrhythmia Fib/FL). We assessed the short-term outcome according to this approach.

Methods:
1462 patients presented to our ED for evaluation of unexplained syncope between September 2007 and September 2009 was prospectively followed. Patients were risk assessed according to the pathway to having SELF-A and SELF-B present (Group A: SELF +/+) or not present (Group B: SELF -/-).The primary endpoint was a composite endpoint of readmission for syncope (ROS), myocardial infarction (MI), stroke or death. Follow-up was 494 ± 120 days.

Results:
762 subjects were classified accordingly to the two groups. 534 (70%) patients in Group A and 228 (30%) patients in Group B. Group A were older (73 ± 15 years vs. 61 ± 21 years), with more hypertension (74% vs. 45%), diabetes (25% vs. 16%), heart failure (9% vs. 3%), and coronary disease (21% vs. 4%); p<0.001. During hospital stay group A had 58 (11%) procedures including 33 device implantation, 10 EP studies, 11 tilt tables and 4 cardioversions. At 7-days follow-up group A patients had 11 (2%) events comparing to 2 (0.01%) for group B; p <0.001. At 30-days follow-up group A patients had 46 (9%) events comparing to 11 (1.7%) for group B; p <0.0001 as seen in Figure.

Conclusions:
Using a simple novel SELF pathway for patients presenting with unexplained syncope effectively identifies high risk patients who merit hospitalization for further work-up. This has important implications for the evaluation management of a common disease that poses a significant economic burden on healthcare utilization.
Abstract 18063: Maternal and Postnatal High-Fat Diet Interaction Leads to Greater Risk of Myocardial Dysfunction in Offspring via Obesity-Induced Lipotoxicity, IRS-1 Serine Phosphorylation and Mitochondrial Defects
Authors: Turdi Subat , Ge Wei , Hu Nan , Bradley Katharine M , Ren Jun
Published: April 2024

Introduction:
Maternal obesity/overnutrition during gestation and lactation are associated with increased prevalence of obesity and cardiovascular risk in adult offspring. Given the pervasive “obesogenic” environment, long-term consequences of maternal and/or postnatal overnutrition on myocardial function warrant immediate attention. Objective: We examined the impact of maternal and long- term postnatal dietary fat exposure on metabolic, myocardial, intracellular Ca2+, insulin and mitochondrial responses.

Methods and Results:
Pregnant FVB mice were fed either a low-fat (LF, 10% of calories) or high-fat (HF, 45% of calories) diet during gestation and lactation. Weaning male offspring were randomized and placed on either LF or HF (a food-restricted HF-fed mice served as weight control group) for 4 months prior to assessment of metabolic indexes, myocardial histology, cardiac function, insulin signaling, mitochondrial integrity and ROS generation. Compared with LF-fed and HF-fed weight-control mice, postnatal HF intake resulted in obesity (DIO), exhibited marked dyslipidemia, blunted insulin sensitivity, cardiac hypertrophy, compromised myocardial function, intracellular Ca2+ homeostasis and mitochondrial biogenesis, all of which were significantly accentuated in postnatal HF-fed mice with maternal high fat exposure.Interestingly, LF-fed offspring from HF-fed dams displayed higher body weights, increased adiposity and dampened insulin sensitivity compared to LF-fed controls. Maternal HF exposure upregulated postnatal HF-induced IRS-1 serine phosphorylation, PTP1B, lipogenic enzyme SCD-1 and hypertrophic markers while downregulating cardiac AMPK signaling and PGC-1α. Importantly, myocardial and mitochondrial ultrastructural abnormalities were more pronounced in HF-fed offspring with maternal HF exposure, as shown by loss of mitochondrial density and membrane potential, increased ROS generation and apoptosis.

Conclusion:
We conclude that prenatal fat exposure may program the offspring at a higher risk for postnatal DIO induced cardiac hypertrophy and dysfunction possibly related to cardiac hypertrophy and lipotoxicity, impaired insulin signaling, mitochondrial dysfunction and oxidative stress.