bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9234: Ventricular Irregularity, but not Ventricular Rate, is Important for Determination of NT-ProBNP Levels in Chronic Atrial Fibrillation: Evidence for Lenient Rate Control in Atrial Fibrillation
Authors: Park Wonjong , Choi Yoon-Jung , Lee Jin-Sung , Kang Min-Kyu , Lee Sang-Hee , Kim Ung , Park Jong-Sun , Shin Dong-gu , Kim Young-Jo
Published: April 2024

Background
Adequate rate control has been a concern in management of patients with atrial fibrillation(AF). Role of ventricular rate(VR) and its irregularity have not been well studied with respect to the elevation of NT-proBNP level. VR at which NT-proBNP level is lowest would be the optimal heart rate in patients with AF.

Methods and Results
In 85 patients with AF(69.8±9.0 years, 43 men), NT-proBNP level, indices of VR irregularity(mean VR, standard deviation(SD) of VR, SD of successive differences and SD of 5-minute averages(SDAVR)) derived from 24-hour ambulatory ECG and transthoracic echocardiographic parameters(early mitral inflow velocity(e)/mitral annular velocity(e′), left atrial volume index and left ventricular ejection fraction(LVEF)) were measured. Potential determinants of NT-proBNP level were identified by univariate and multivariate linear analysis. Age, e/e’ and SDAVR were significant univariate predictors of NT-proBNP level, but mean VR did not. e/e′and SDAVR remained as significant predictors after multivariate adjustment(β=0.028,
P
=0.004, and β=-0.002,
P
=0.008, respectively). When the patients were stratified with the 33rd and 67th percentile values of e/e′(10.62 and 14.63, respectively), a significant positive correlation between mean VR and NT-proBNP level was present in patients with higher e/e(N=57, β=0.007,
P
=0.043).

Conclusions
LV diastolic function and VR irregularity rather than VR were associated with elevation of NT-proBNP level in AF.

Key words
: Atrial fibrillation, NT-proBNP
Abstract 9240: Activation of PPARγ Converts the Mechanism of Flow-Mediated Dilation in Human Microvessels from H2O2 to NO by a Telomerase Dependent Mechanism
Authors: Beyer Andreas M , Gutterman David D
Published: April 2024

Reactive oxygen species (ROS) are important modulators of vascular reactivity. Coronary artery disease (CAD) changes the mechanism of human arteriolar flow-mediated dilation (FMD) from NO to hydrogen peroxide (H2O2), a signaling ROS. Increasing evidence shows that mitochondrial ROS (mtROS) production and the longevity of a cell or organism are inversely related. Telomerase activity (TA), prominent in cellular senescence and tissue aging, shows a reciprocal relationship with mtROS production. Rosiglitazone (Rosi) activates peroxisome proliferator-activated receptor γ (PPARγ) resulting in increased telomerase expression. This could mitigate mtROS production, leading to increased NO bioavailability, improved vascular function, and retardation of atherosclerosis. We hypothesized that PPARγ reduces elevated ROS levels in CAD and converts the mechanism of FMD from H2O2 to NO by increasing telomerase activity.

Human adipose arterioles (~200 µm) from discarded pericardial tissue were cannulated for videomicroscopy. Dilation to graded degrees of shear was measured in vessels constricted with endothelin-1. Pharmacological inhibition of TA (BIRBR 1532 10 μM 15-20 h) in vessels from healthy individuals shifted the mechanism of FMD from NO to H2O2 (Panel A+B). In arterioles from patients with CAD, Rosi (10 μM 15-20 h) shifted the mechanism of FMD from H2O2 to NO (Panel C). In vessels from patients with CAD, BIBRB1532 prevented the ability of Rosi to convert the mediator of FMD from NO to H2O2 (D). We conclude that PPARγ signaling increases telomerase activity in the vasculature, which plays a critical and acute role in modulating microvascular function.
Abstract 9299: Gender Differences in Factors Influencing Electrocardiographic Findings of Left Ventricular Hypertrophy in Severe Aortic Stenosis
Authors: Satoh Shinji , Omura Soichiro , Inoue Hiroko , Nohara Yume , Ito Shogo , Mori Takahiro , Takenaka Katsuhiko , Numaguchi Kotaro , Mori Etsuo , Aso Akemi , Nakamura Toshihiro , Hiyamuta Koji
Published: April 2024

Background:

Functional and geometric responses of left ventricule (LV) to chronic pressure overload, such as hypertension and aortic stenosis (AS), have been reported to be different between genders. However, gender differences in factors influencing ECG findings of LV hypertrophy (LVH) in pressure overload are unknown yet.

Methods:

We conducted a prospective observational study in patients with isolated severe AS (aortic valve area [AVA] <1.0cm
2
; n: men 35, women 68). ECG LVH criteria were classified into the following three categories: 1) high voltage by the Sokolow-Lyon index associated with ST-T wave change (no digitalis); 2) only high voltage; and 3) normal. Groups 1) and 2) were defined as LVH on ECG. We compared the ECG findings in relation to AS severity between genders.

Results:

Women were older with no significant differences in prevalence of hypertension, AVA index (AVAI), mean peak pressure gradient or peak velocity, LV mass index (LVMI), or the distribution of ECG categories between genders (Table). Multiple logistic regression analysis including of age, gender, hypertension, AVAI, mean pressure gradient, and LVMI revealed that LVMI (p=0.001) and AVAI (p=0.0434) significantly related to the ECG categories. LVMI significantly predicted LVH on ECG in both genders, but AVAI did only in women (Figure).

Conclusions:

The ECG LVH in severe AS may be mainly determined by LVMI in men and by both LVMI and AVAI in women. ECG may reflect AS severity better in women than in men.phic_{9D8EC702-4573-41EF-9F9E-1A8D62620A97}$$
Abstract 9300: Gene Polymorphisms In Il-10 And Inf-γ are Associated With Early Atherosclerosis In Coronary but not in Carotid Arteries: A Study Of 122 Autopsy Cases of Young Adults
Authors: Faffe Débora S , EsperanÇa José Carlos P , Miranda William R , Netto José B , Lima Fabiane S , Urményi Turán P , Silva Rosane , Cabello Pedro H , Rondinelli Edson
Published: April 2024

Atherosclerosis is a complex disease that involves both genetic and environmental factors. However, the influence of genetic variations to its early development remains unclear. We examined the association of single-nucleotide polymorphisms (SNPs) with atherosclerotic severity in the anterior descendent coronary (DA, n=103) and carotid arteries (CA, n=66) in individuals under 30 years autopsied at the Legal Medical Institute of Rio de Janeiro. Histological sections, stained with hematoxilin-eosin, were classified for atherosclerosis severity accordingly to the American Heart Association. SNPs in the ECA, TNF-α (-308G/A and -238 G/A), IFN-γ (+874 A/T), MMP-9 (-1562 C/T), IL-10 (-1082 A/G and -819 C/T), NOS3 (894 G/T), ApoA1 (
rs964184
), and ApoE (E2E3E4 isoforms) genes were genotyped by automatic sequencing. Population mean age was 26 years (107 males and 15 females). DA and CA histology showed, respectively: normal arteries in 2 and 1 cases; level I atherosclerotic lesion in 0 and 5; level II in 16 and 12; level III in 71 and 26; level IV in 6 and 19; and level V in 8 and 3 cases. Genotype distribution was as follow: ECA: 49 DD (related to high ECA levels), 18 II (related with low ECA levels) and 48 DI; TNF-α: 59 GG, 21 GA, and 8 AA at position -308 (allele A associated with high TNF-α level), and 84 GG, 3 GA, and 2 AA at position -238; INF-γ: 45 subjects with allele T (related to high INF-γ levels); MMP-9: 49 CC, 14 CT, and 3 TT; IL-10: 31 AA, 10 AG, and 7 GG at position -1082 (allele G related to high IL-10 levels), and 25 CC, 12 TC, and 15 TT at position -819; NOS3: 59 GG, 35 GT, and 0 TT; ApoA1: 55 CC, 39 CG, and 0 GG; ApoE: 56 E3E3, 30 E3E4, 12 E2E3, 1 E2E4, and 1E4E4. IFN-γ and IL-10 (-1082 A/G) were significantly related to atherosclerotic severity in DA artery, while no association was observed for CA. In conclusion, we observed a high prevalence of early atherosclerosis in young adults, with significant association of IFN-γ (p < 0.001) and IL-10 (p = 0.013) genotypes with coronary disease severity.
Abstract 9303: C-Reactive Protein Trends and Associations with Total Mortality in United States Adults between 1999-2010
Authors: Ong Kwok Leung , Allison Matthew A , Cheung Bernard MY , Wu Ben J , Barter Philip J , Rye Kerry-Anne
Published: April 2024

Introduction:
C-reactive protein (CRP) is a well-known biomarker of systemic inflammation. Elevation of CRP levels is predictive of incident cardiovascular disease morbidity and mortality. We investigated the trends in prevalence of elevated CRP levels (x003E;3.0 mg/L), as well as mean CRP levels, in a general population of United States adults and then determine the associations with mortality.

Methods:
Data from the 27,214 subjects aged ≥20 years in the National Health and Nutrition Examination Survey (NHANES) 1999-2010 were analyzed. Among them, 12,259 subjects from NHANES 1999-2004 had mortality data followed up through December 31, 2006.

Results:
After adjusting for age, sex, race/ethnicity, body mass index, and medications for lowering blood pressure, glucose and lipids, the prevalence of elevated CRP decreased significantly from 36.7% in 1999-2002 to 32.0% in 2007-2010, corresponding to a decrease in mean CRP levels from 1.92 to 1.66 mg/L (both
P
<0.001). The trend remained significant after additional adjustment for several traditional cardiovascular risk factors and use of medications, including statins, angiotensin-converting enzyme inhibitors, metformin, aspirin and clopidogrel. However, the decreasing trends were attenuated after additional adjustment for total bilirubin (
P
=0.076 and 0.024), which increased from 0.62 to 0.73 mg/dL over 12 years (
P
<0.001). Of note, higher CRP levels were modestly associated with a higher risk of total mortality (adjusted hazard ratio: 1.07 [95%CI, 1.03-1.12] per 10 mg/L increase,
P
=0.001), and this association tended to be stronger in subjects with higher total bilirubin levels (
P
for interaction<0.001).

Conclusion:
The decreasing trend of CRP levels is encouraging and may be related to the increase in total bilirubin levels. Such trends may be explained in part by the increasing use of some medications such as statins that can increase bilirubin levels and decrease CRP levels. Moreover, the prediction of total mortality by CRP levels seems to be stronger in subjects with higher total bilirubin levels.
Abstract 9356: Pre-procedure C-reactive Protein and Erythrocyte Sedimentation Rate but not Lipoprotein-associated Phospholipase A2 Predict Clinical Outcomes after Drug-eluting Stents Implantation in Patients with Stable Coronary Disease on Chronic Statin Therapy
Authors: Karpov Yuri , Buza Vitaly
Published: April 2024

Background:
Pre-procedure high-sensitive C-reactive protein (hs-CRP) level has a prognostic value after PCI. There are few data about the value of other inflammation markers: lipoprotein-associated phospholipase A2 (Lp-PLA2), erythrocyte sedimentation rate (ESR), white blood count (WBC) in predicting periprocedural and long-term outcomes after drug-eluting stent (DES) especially in patients on chronic statin therapy.

Methods:
A total of 602 patients (mean age 60.4±9.4 years, 86.0 % males) with stable CAD on chronic statin therapy underwent successful PCI with at least one DES implanted. Baseline demographic, procedural characteristics, Lp-PLA2, hs-CRP, ESR, WBC were collected. Tn I was assessed in all patients 12-18 h after the PCI. Periprocedural MI was defined as measure of the Tn I of more than three times the 99th percentile of the upper reference limit. The patients were prospectively followed before discharge with 1 year of follow-up.

Results:
During the in-hospital period major adverse cardiovascular events (MACE) (death, myocardial infarction (MI), stroke, stent thrombosis (ST)) occurred in 10.6% of the patients. Incidence of MACE was essentially due to periprocedural MI (10,3%). Multivariate logistic regression identified ESR level (OR 1.018 95% CI 1.004-1.032, p=0.013) before PCI and total length of stents implanted (OR 1.023, 95% CI 1.008-1.037, p=0.002) as independent predictors of MACE before discharge. At 1 year of follow-up MACE (death, MI, [[Unable to Display Character: с]]linically-driven target lesion revascularization (TLR)) occurred in another 9.3% of the patients. TLR was performed in 5.4% of the patients. Multivariate logistic regression identified baseline hs-CRP (OR 1.7, 95% CI 1.13-2.56, p=0.01) and ESR (OR 2.25, 95% CI 1.21-4.19, p = 0.011) levels, stenting CABG grafts (OR 8.34, 95% CI 1.95-35.6, p = 0.004) as independent predictors of MACE at 1 year. hs-CRP (OR 1.75, 95% CI 1.15-2.67, p = 0.009) and ESR (OR 2.42, 95% CI 1.15-5.13, p = 0.02) levels were independent predictors of TLR at 1 year. WBC and Lp-PLA2 were not predictive of MACE neither acutely nor at 1 year.

Conclusion:
Pre-procedure CRP and ESR but not Lp-PLA2 and WBC levels correlate with clinical outcomes including TLR in patients with stable CAD on chronic statin therapy undergoing DES implantation.
Abstract 9371: Low In-Treatment HDL Cholesterol Strongly Predicts Incident Atrial Fibrillation: The LIFE Study
Authors: Okin Peter M , Hille Darcy A , Wachtell Kristian , Kjeldsen Sverre E , Dahlöf Björn , Devereux Richard B
Published: April 2024

Background:
Hypertensive patients are at increased risk of atrial fibrillation (AF). Although low baseline HDL levels have been associated with a higher risk of AF in some analyses, this has not been born out in recent population-based studies; whether changing levels of HDL over time are more strongly related to the risk of new AF has not been examined.

Methods:
Incident AF was examined in relation to baseline and in-treatment HDL levels prior to development of AF in 8267 hypertensive patients with no history of AF, in sinus rhythm on their baseline ECG, randomly assigned to losartan- or atenolol-based treatment. HDL levels at baseline and each year of testing were categorized into quartiles according to baseline HDL levels.

Results:
During 4.7±1.1 years follow-up, new AF developed in 645 patients (7.8%). In univariate analyses, compared with HDL >1.78 mMol/L, patients with in-treatment HDL <1.21 entered as a time-varying covariate had a 53% greater risk of new AF; patients with in-treatment HDL in the 2
nd
or 3
rd
quartiles had intermediate increased risks of AF. Baseline HDL was only a weak predictor of new AF. In multivariate Cox analyses adjusting for multiple AF risk factors, including the previously demonstrated predictive value of in-treatment heart rate and Cornell product LVH, there was no attenuation of the risk of new AF associated with low in-treatment HDL. In-treatment non-HDL cholesterol (p=0.171) and statin use (p=0.626) were not significant predictors of new AF in the multivariate model including in-treatment HDL. Baseline HDL was not a significant predictor of AF in multivariate analysis.

Conclusions:
Lower in-treatment HDL is strongly associated with risk of new AF, even after adjusting for other potential AF risk factors and treatment effects. These findings suggest that serial assessment of HDL can better estimate AF risk in hypertensive patients. Further study is indicated to determine whether therapies that increase HDL can lower risk of developing AF.
Abstract 9386: Attenuation of Post-infarct Cardiac Hypertrophy by Allogeneic Cell-mediated Supplemental Igf-1 Propeptide Delivery
Authors: Santini Maria Paola , Poudel Bhawana , Poggioli Tommaso , Bilbao Daniel , Zarrinpashneh Elham , Sarathchandra Padmini , Rosenthal Nadia
Published: April 2024

Background:
Cardiovascular remodelling after myocardial infarction leads to cardiac function impairment due to left ventricle dilation, distortion of ventricular shape and mural hypertrophy. Therefore, ventricular remodelling can be considered a primary target for therapeutic treatment. We previously documented that cardiac-specific overexpression of the propeptide insulin-like growth factor 1Ea (IGF-1Ea) contributed to beneficial cardiac repair after ischemic damage by employing anti-inflammatory and antioxidant molecules, decreasing scar formation and enhancing cardiac function. The above benefits suggest that IGF-1 may be therapeutically important in cardiovascular diseases. However, the precise mechanisms in clinical-like procedures are not yet elucidated and IGF-1 family of growth factors are therefore poorly recognized pharmacologically. We hypothesized that IGF-1Ea-mediated delivery by allogeneic cell therapy could favour long-term decrease of left ventricle remodelling after myocardial infarction.

Methods and Results:
To support long-term expression of the propeptide IGF-1Ea, we infected pluripotent P19Cl6-MLC2vGFP cells with a lentivirus carrying the Igf-1Ea gene under the CMV promoter. These cells, which efficiently differentiate into cardiomyocytes activating a GFP transgene, were injected into the ventricular wall of C57BL/6 mice (n=11) after myocardial infarct induction in an allogeneic transplantation model. Mice injected with cells not expressing the transgene were used as control. IGF-1Ea delivery improved long-term local systolic function measured as percentage of anterior wall motion (60% vs 20%, p<0.01) and correlated with increased cell retention, decreased hypertrophic response through downregulation of the angiotensin signalling and activated pro-angiogenic program compared to mice transplanted with cells not expressing the transgene.

Conclusions:
this study indicates that allogeneic cell-mediated IGF-1Ea delivery is a good candidate in pharmacological and clinical studies to contribute to long-term beneficial remodelling of the heart in response to myocardial infarct.
Abstract 9463: Septal Myocardial Function is reduced in Carriers of Lamin A/C mutations and related to Atrioventricular Block, Ventricular Tachycardia and Septal Fibrosis
Authors: Hasselberg Nina E , Edvardsen Thor , Petri Helle , Berge Knut E , Leren Trond P , Bundgaard Henning , Haugaa Kristina H
Published: April 2024

Background:
Mutations in the Lamin A/C gene may cause dilated cardiomyopathy accompanied by atrioventricular (AV) block, atrial fibrillation and ventricular tachycardia (VT). VTs are frequent and commonly occur before development of dilated cardiomyopathy. Mechanisms of AV block and VT in these patients are not fully understood.

Methods:
We included 41 Lamin A/C mutation carriers with LV (left ventricular) EF 55±13%. PR interval from resting ECG and occurrence of VT by Holter monitoring and ICDs were recorded. Global and LV septal myocardial function were assessed by echocardiographic speckle tracking strain analysis. Nine patients were eligible for magnetic resonance imaging (MRI) with late gadolinium enhancement (LGE) to assess presence and distribution of myocardial fibrosis.

Results:
VT was documented in 21 patients (51%). Prolonged PR interval (p<0.001), presence of AV block (p<0.001) and reduced global longitudinal strain (p=0.01) were markers of VT, while LVEF was not (p=0.55). LV septal function was markedly reduced compared to function in the rest of the left ventricle (strain -16.7% vs. -18.7%, p=0.001). Prolonged PR interval correlated with reduced LV septal function (R=0.41, p=0.03). By LGE MRI, 4/5 patients (80%) with documented VT showed LV septal fibrosis while no fibrosis was detected in 4/4 (100%) patients without VT (p=0.05). Fibrosis by MRI was located exclusively in the LV septum. PR interval was longer in patients with LV septal fibrosis compared to those without (320±26 vs. 172±66ms, p=0.002).

Conclusion:
In Lamin A/C mutation carriers, myocardial function was most decreased in the LV septum and correlated to prolonged PR interval. Prolonged PR interval was a marker of VT. Myocardial LV septal fibrosis was associated with prolonged PR interval and VT. Localized fibrosis in the LV septum may be the mechanism behind AV block, VT and reduced LV septal function in Lamin A/C mutation carriers.
Abstract 9481: The Response of the Qt Interval and the T-wave Morphology to Sudden Tachycardia Provoked by Standing in Young Athletes
Authors: Menafoglio Andrea , Di Valentino Marcello , Gallino Augusto
Published: April 2024

Background:
the response of the QT interval to the sudden tachycardia provoked by standing can aid in the diagnosis of the long QT syndrome (LQTS). It is therefore important to know what is the normal response to this maneuver. The aim of this study was to characterise the response of the QT interval and the T-wave morphology following this provocation test in young healthy athletes.

Methods:
ECG was analysed as part of a prospective study about the impact of cardiovascular screening with ECG in young (14-35 years) athletes. ECG was performed after 5 minute of supine resting. Athletes without cardiac abnormalities, not taking drugs and with normal ECG (QTc for men < 450 msec, for women < 460 msec) were asked to stand up quickly with continuous ECG monitoring for 30”. Heart rate, QT, QTc (Bazett) and T-wave morphology [normal, biphasic, notched G1 (T2>T1), notched G2 (T2>>T1)] were analysed at baseline and at maximal tachycardia.

Results:
ECG of 289 athletes was analysed (76 % men, mean age 18.4 ± 5.6 years). Baseline parameters were following: heart rate 69 ± 11/min, QT 378 ± 27 msec, QTc 401 ± 21 msec. After standing, the maximal heart rate was 101 ± 13/min. QT was 361 ± 28 msec (shortening by 17 ±11 msec). In 4 % of athletes QT increased by 10-20 msec. QTc was 466 ± 30 msec (lengthening of 65 ± 24 msec). In 12 % of athletes QTc was ≥ 500 msec. T-wave morphology during tachycardia were notched G2 in 6% of athletes. During tachycardia, 15 % of athletes displayed a QTc ≥ 500 msec or QT lengthening or notched G2 morphology of T waves.

Conclusions:
During sudden tachycardia, a significant proportion of healthy young athletes demonstrated QTc interval and changes of T-wave morphology in the magnitude observed in patients with the LQTS. Caution should be applied in interpreting these parameters in ECG tracing and Holter monitoring displaying sudden oscillations of heart rate in this population.
Abstract 9507: Noise vs. Signal: The Clinical Implications of A High Sensitivity Troponin Assay in the Evaluation of Possible Acute Coronary Syndrome
Authors: Wolf Sarah Y , Kaur Ramanjit , McKeown William Patrick , Chan Helen , Dang Allen , Kuston Trevor , Leung Waihin , Purakal John , O'Neil Brian J , Williams Kim A , Levy Phillip D
Published: April 2024

Objectives:
To evaluate the real-world impact of a switch from conventional troponin I (cTnI) measurement to a high-sensitivity (hsTnI) assay in patients with acute coronary syndromes (ACS).

Methods:
This was a retrospective analysis of ACS cases from a single hospital system in the 3 months before and after a troponin assay switch. Outcomes included admitting diagnosis, initial treatment and diagnostic testing, need for coronary artery intervention (i.e., stent placement), in-hospital events, and final discharge diagnosis. Descriptive statistics and univariate comparisons by assay group were performed.

Results:
783 ACS cases (mean age 60.9 yrs; 52.9% male; 77.7% black) were identified, 330 (42.1%) before and 453 (57.9%) after the assay change with no difference in demographics by assay period. An admitting diagnosis of NSTEMI was more common after the assay change (43.0% vs. 70.4%; p < 0.001) as was the proportion with a positive troponin (32.1% vs. 71.3%; p < 0.001). While aspirin (92.4% vs. 91.4%; p = 0.79), beta-blocker (76.1% vs. 80.8%; p = 0.09) and clopidogrel (50.9% vs. 46.6%; p = 0.25) use was similar, anticoagulants were used more often after the assay change (45.8% vs. 56.3%; p = 0.004). Echocardiography was also more common (39.7% vs. 47.0%; p = 0.05), but cardiac catheterization was less frequent (53.6% vs. 41.7%; p = 0.003) with no difference in the proportion who underwent stent placement (52.4% vs. 50.0%; p = 0.72). In-hospital event rates (Table) were equivalent. At discharge, diagnosis of NSTEMI was more likely post-assay change (27.9% vs. 36.6%; p = 0.011).

Conclusions:
After the switch to a hsTnI assay, more ACS patients had a positive test result and a greater proportion were diagnosed with NSTEMI at admission. Despite this, cardiac catheterization was used less frequently and coronary artery intervention as well as in-hospital event rates were flat, highlighting the uncertainty that surrounds a positive troponin in an era of high-sensitivity assays.
Abstract 9536: Computed Tomography Derived Cardiovascular Risk Markers, Incident Cardiovascular Events and All- Cause Mortality In Adults Free of Clinical Cardiovascular Disease. The Multi Ethnic Study of Atherosclerosis
Authors: Yeboah Joseph , Carr Jeffery J , Terry James G , Ding Jingzhong , Zeb Irfan , Liu Songtao , Nasir Khurram , Post Wendy , Blumenthal Roger S , Budoff Mathew
Published: April 2024

Introduction:
Cardiac CT derived CV risk markers such as coronary artery calcium (CAC), thoracic wall calcium (TAC), aortic valve calcium (AVC), mitral valve calcium (MVC), pericardial adipose tissue volume (PAT) and liver attenuation (LA) have all been associated with CV risk and events. However, there is no head to head comparison of these markers in a single sample using the same statistical approach, and it remains unclear whether a combination of these markers can further improve CV risk prediction. We assessed the predictive value of CAC, TAC, AVC, MVC, PAT, LA and a combination of these markers for incident CVD/CHD/mortality in MESA.

Methods:
After 9 years of follow up, 327 had adjudicated CHD defined as MI, angina if followed by PTCI/CABG, cardiac arrest or CHD death, 457 had CVD events defined as CHD, stroke/TIA or CVD death and 398 died. Cox proportional hazard, area under curve(auc) and net reclassification improvement (NRI) analyses were used adjusting for age, gender, race, SBP, total and HDL cholesterol, triglycerides, BMI, smoking, BP med and statin use.

Results:
6591 MESA participants mean age and BMI, 62 years and 28.4 kg/m
2
, 53% females, 38% Caucasians, 28% African Americans, 22% Hispanics and 11% Chinese. Unlike PAT and LA; CAC, TAC, AVC and MVC were all significantly associated with incident CVD/CHD/ mortality in our multivariable Cox model with CAC having the strongest association. CAC had the highest AUC when used alone to predict incident CHD/CVD whilst LA had the least. The addition of CAC to Framingham Risk Score (FRS) resulted in the most improvement in AUC for incident CVD (0.721 vs. 0.766, p<0.0001) and CHD (0.712 vs. 0.766, p<0.0001). The addition of CAC to the FRS resulted in an NRI of 0.191 for incident CVD and 0.229 for incident CHD. The addition of TAC, AVC, MVC, PAT and LA individually to FRS + CAC resulted in little further improvement in AUC/NRI for the prediction of CHD/CVD. Similar results were obtained when the analysis was limited to participants with intermediate FRS. Any other combination of risk markers yielded inferior results.

Conclusion:
CAC is superior for improving CV risk prediction over and beyond the FRS. The addition of TAC, AVC, MVC, PAT and LA only minimally improves the predictive accuracy afforded by the combination of FRS and CAC.
Abstract 9542: HDL is Dysfunctional in Patients with Ischemic Cardiomyopathy
Authors: Patel Parin J , Khera Amit V , Rader Daniel J
Published: April 2024

Objectives:
Various pathologic changes lead to the development of systolic heart failure. We previously showed that HDL is dysfunctional in both acute coronary syndrome (ACS), as measured by the HDL inflammatory index (HII) assay, and stable CAD, as measured by cholesterol efflux capacity. We therefore hypothesized that these functions of HDL are also impaired in subjects with ischemic heart failure.

Methods:
A nested case-control study was performed on subjects in the PennCath cohort of patients with angina undergoing cardiac catheterization. Cases had ejection fraction (EF) less than 55% (measured by ventriculography) and angiographic CAD (≥20% stenosis of any vessel; n=23); controls included those with EF≥55% and no CAD (n=46). The HII and cholesterol efflux assays were performed as previously described. Briefly, apo-B depleted serum from subjects was incubated with either oxidized LDL and a lipid substrate that fluoresces when oxidized, or macrophages and tritium-labeled cholesterol. Impaired anti-oxidative capacity corresponds with a higher HII value, and reduced cholesterol efflux capacity corresponds with lower percent efflux.

Results:
Mean HII was higher in subjects with ischemic heart failure (0.26 v. -0.028; p = 0.012); mean cholesterol efflux was lower in the same population (0.80 v. 0.92; p = 0.021). Subjects with ischemic heart failure also had more incident diabetes and hypertension, worse renal function, and lower HDL mass. In a multivariable linear regression model for risk factors of heart failure, both high HII and low efflux capacity were significant risk factors (Table).

Conclusion:
Subjects with ischemic cardiomyopathy have lower HDL mass and also impaired HDL function. This research supports prior findings of dysfunctional HDL in nonischemic cardiomyopathy, ACS, and chronic CAD. HDL is a versatile molecule with various anti-inflammatory and vasoprotective functions, whose impairment may contribute to heart failure.
Abstract 9595: A Novel Niacin Analog (ARI-3037MO) Induces Favorable Plasma Lipid Changes Without Flush in Single and Multiple Ascending Dose Placebo Controlled Trials in Normal Healthy Volunteers
Authors: Benedict Claude , Neutel Joel , Bachovchin William , Kiritsy Christopher
Published: April 2024

INTRODUCTION: Despite niacin’s (NA) beneficial effects on lipids, it’s use is limited by side effects, such as flushing, itching, and increases in liver enzymes and blood glucose. These effects, particularly flushing, lead to poor compliance and persistence in clinical use. ARI-3037MO is an orally active, novel, NA analog that produces significant lipid altering effects at least as effective as NA on low density lipoproteins (LDL-C), triglycerides (TG) and high density lipoproteins (HDL-C) in preclinical studies without flushing.

METHODS: To evaluate safety and pharmacokinetics of ARI-3037MO in humans, we conducted a single ascending dose (SAD) trial and a multiple ascending dose (MAD) trial in healthy volunteers. In SAD study, five doses of ARI-3037MO QD were evaluated in 30 subjects (n=6 per dose; 17 males, 13 females). Ten additional subjects received matching placebo. In MAD trial, four doses of ARI-3037MO [(0.5g (n=8), 1g (n=8), 2g (n=9) & 3.5g (n=9)] QD were evaluated in 34 healthy volunteers (24 males, 10 females) for 14 or 28 days (2g QD cohort only). Eight additional subjects received matching placebo. RESULTS: In SAD trial all doses (0.5g - 6g/day) of ARI-3037MO, were well tolerated with no evidence of flushing, itching or other skin changes even at the 6g QD dose. No liver function or glucose abnormalities were observed. There was a reduction in TG (-56.7 +/- 37.0 mg/dl; mean+/- SEM; p < 0.05 ANOVA) and an increase in HDL-C (+ 7.7 +/- 1.6 mg/dl; p < 0.05 ANOVA) in the 6g cohort. In MAD trial, all doses were well tolerated with no evidence of flushing, itching or other skin changes even at the highest dose. No liver function or glucose abnormalities were observed. There was a significant reduction in TGs with 2g dose given for 28 days as well as a trend toward reduction in LDL-C. Following single or multiple dosing, ARI-3037MO was rapidly absorbed and plasma drug levels showed good dose proportionality. CONCLUSION: The absence of any adverse effects (including flush, increases in liver enzymes and blood glucose) at all doses in the SAD and MAD studies, combined with encouraging lipid effects in these short duration trials indicates that ARI-3037MO represents a potential transformational niacin-based therapy for patients with dyslipidemia and metabolic syndrome.
Abstract 9598: A Focused Heart Failure Self-Care Intervention Improves Self-Care Behavior Even in Patients with Global Cognitive Dysfunction
Authors: Moser Debra K , Pelter Michele M , Nesbitt Tom , Biddle Martha J , Robinson Susan , SOUTHARD Jeffrey
Published: April 2024

Heart failure (HF) patients have high rates of global cognitive dysfunction (GCD). HF requires challenging levels of self-care for all, but may be particularly difficult for those with GCD. Objective: Determine the impact of tailored intervention focused on improving self-care of symptom management in HF patients with or without GCD. Methods: We randomized 614 (41.2% female; age 66 ± 13 years; 35.4% NYHA class III/IV) rural patients with HF to usual care or one of two active self-care symptom monitoring and management intervention groups (i.e., LITE and PLUS). Both intervention groups included tailored (to address individual barriers to self-care) education and counseling providing skills to recognize symptoms of escalating HF, tools to monitor symptoms and motivation to respond early. Intervention was delivered by an expert HF nurse. Intervention groups differed only in contact frequency; LITE group received two follow-up calls, while PLUS group received bi-weekly calls until judged trained. Cognitive function was assessed at baseline using the Mini-Cog; scores range from 0 to 6. Patients with overt dementia were excluded. GCD was defined as a score of 3 or 4. Self-care outcome data (HF Self-Care Behavior Scale) were collected at baseline, 3 and 12 months. Data were analyzed using repeated measures ANCOVA, controlling for age and education level. Findings: Of enrollees, 33.7% met criteria for GCD. Self-care improved in both intervention groups, but worsened in the usual care group (p < 0.001 for group by time interaction). Patients with and without GCD demonstrated improvements in self-care when assigned to either of the intervention groups, but not the usual care group (Figure).

Conclusion:
Individualized intervention that includes focus on HF patients’ barriers to engaging in self-care is effective in improving self-care even in patients with GCD. A higher intensity of contact was not needed to achieve this effect.
Abstract 96: Healthcare Disparity: Post--Cardiac Arrest Care Knows No Color Barriers
Authors: Eid Shaker M , Albaeni Aiham , Vaidya Dhananjay , Chandra-Strobos Nisha
Published: April 2024

Background:
A clinical manifestation of several diseases (e.g. Diabetes Mellitus, Hypertension, and Coronary Artery Disease) in African-Americans and other non-Caucasian populations is cardiac arrest. Since many studies have confirmed healthcare disparities in patients of color, we explored whether cardiac arrest care varied by race in a large metropolitan hospital drawing from a diverse population of over half a million (38% non-Caucasian 35% African-American) served by a diverse physician group.

Methods:
We evaluated 170 survivors of non-traumatic out-of-hospital cardiac arrest (age 63 ± 16, 62.4% males). To index appropriateness and vigor of resuscitation and post-arrest care, we studied the factors listed in the table below together with: hypothermia therapy, withdrawal of care and survival to discharge in Caucasians vs. Non-Caucasians. Data were analyzed using Chi-square test and T-test. Data are reported as percentage, mean and standard deviation or median and 25
th
/75
th
quartiles.

Results:
Of 170 patients, 47 were non-Caucasian with 44 being African-American and 3 Hispanic. The incidence of VF/VT was comparable in Caucasians and non Caucasians as was the time to Return of Spontaneous Circulation (ROSC), the use of epinephrine, or therapeutic hypothermia. Similarly, care delivery was comparable with no difference in the length of hospital stay, use of testing, withdrawal of support or early care withdrawal. There was a trend to a greater likelihood of bystander CPR in non Caucasians; however, survival to discharge or neurological status was not affected, and remained comparable in both patient groups.

Conclusion:
These data demonstrate that irrespective of healthcare disparities that may exist early during disease, following cardiac arrest, therapy is color blind.
Abstract 9626: Tolerability of Apixaban-Insights From A Meta-Analysis of Discontinuation Rates in Randomized Trials
Authors: Kundu Ria , Chatterjee Saurav , Ghose Abhimanyu , Sharma Abhishek , Ghosh Joydeep
Published: April 2024

Background:
Apixaban is one of the most promising newer oral anti-coagulant agents being considered as a viable alternative for warfarin. However tolerability of the new drug, as reflected by rates of discontinuation in randomized trials for various indications, is conflicting. Objective: To evaluate the tolerability of apixaban by assessing discontinuation rates in trials of apixaban.

Methods:
A search was made of the PubMed, CENTRAL and EMBASE databases for randomized controlled trials that reported discontinuation rates of apixaban and comparator (could be pharmacologically active or not). The random effects (DerSimonian-Laird) Mantel-Haenszel (M-H) test was used to compare discontinuation rates of apixaban against comparators by evaluating relative risk (RR; 95% confidence interval [CI]). Statistical analysis was done with Review Manager V5.1 .

Results:
Analysis of eight RCTs (N=43277) revealed no significant increase in risk of discontinuation with apixaban compared to a variety of comparators (RR 1.09, 95% CI 0.91-1.30). On restricting the analysis to pharmacologically active agents, there was a definite trend towards improved discontinuation rates with apixaban, compared with warfarin, enoxaparin and aspirin (RR 0.95, 95% CI 0.90-1.00), without evidence of significant heterogeneity.

Conclusion:
Apixaban is well tolerated, when compared against a variety of comparators, as evidenced by comparable discontinuation rates in randomized trials.

Figure: Forest Plot of Relative Risk of Discontinuation of Apixaban Compared with All and Pharmacologically Active Comparators in Randomized Trials
Abstract 9638: Left Atrial Volume Provides Independent and Incremental Prognostic Information in Non-Ischemic Dilated Cardiomyopathy
Authors: Gulati Ankur , Ismail Nizar , Ismail Tevfik , Ali Aamir , Liodakis Emmanouil , Morarji Kishen , Guha Kaushik , Baksi Arun J , Krishnathasan Kaushiga , Roughton Michael , Pakrashi Tapesh , Alpendurada Francisco , Jabbour Andrew , Pennell Dudley J , Prasad Sanjay K
Published: April 2024

Introduction:
Echo data have shown that left atrial (LA) diameter and area predict adverse outcome in heart failure (HF) cohorts of mixed etiology. Since LA dilatation is asymmetric, LA volume (LAV) is a better measure of LA size. CMR allows more accurate measurement of LAV due to its superior spatial resolution and endocardial border definition. We hypothesized that CMR assessment of LAV provides independent and incremental prognostic information in non-ischemic dilated cardiomyopathy (DCM).

Methods:
Consecutive patients with DCM referred for CMR between 2000-08 were prospectively enrolled. Patients with IHD, primary valvar disease and infiltrative CM were excluded. LAV was measured at LV end-systole by a single blinded specialist using the biplane area-length method and indexed to body surface area (LAVi). The primary endpoint was cardiovascular (CV) death or cardiac transplantation (CTx). The secondary endpoint was a composite of HF death, HF hospitalization or CTx.

Results:
In total 483 patients (327 male, mean age 51 yrs, mean LVEF 37%) were followed up for a median duration of 64 months. There were 75 deaths (60 CV deaths) and 9 patients underwent CTx. ROC analysis identified that the optimal LAVi cut-off value for predicting the primary endpoint was 77 ml/m
2
. Kaplan-Meier analysis demonstrated that patients with a LAVi>77 ml/m
2
had a significantly higher rate of CV death or CTx (p<0.001, Fig.1). After stepwise Cox regression multivariate analysis, LAVi remained a significant independent predictor of CV death or CTx (HR per 10 ml/m
2
, 1.11, 95% CI 1.04 to 1.19; p=0.003) and the secondary HF composite (HR per 10 ml/m
2
, 1.11, 95% CI 1.04 to 1.18; p=0.001), alongside conventional prognosticators such as LVEF and NYHA class.

Conclusions:
LAV has independent and incremental prognostic value for the prediction of transplant-free CV survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.
Abstract 9672: Older Age at Fontan is Associated with Improved Exercise Performance in the Current Era
Authors: Bolin Elijah H , Maskatia Shiraz , Tate Amanda , Payne William , Petit Christopher J
Published: April 2024

Introduction:
Exercise capacity is associated with mortality and morbidity in Fontan patients. Debate continues about modifiable factors impacting exercise.
Hypothesis:
We assessed the hypothesis that later Fontan completion and larger branch pulmonary arteries are associated with better exercise.

Methods:
We performed a retrospective review of exercise stress test (EST) data from 2003 to 2011 in Fontan patients undergoing the Bruce protocol. The primary marker of performance was percent of predicted maximum oxygen consumption (%MVO
2
). Pulmonary artery caliber was assessed using tomographic or angiographic imaging, and included if imaging was performed four years before or after the EST. Imaging or catheterization data were excluded if surgical or catheterization based interventions were performed such that a patient's anatomy changed between the time of EST and imaging. Analysis was performed on the entire cohort and a Current Era group defined as patients who underwent Glenn ≤ 1 year, did not have a pacemaker at EST, and achieved a respiratory exchange ratio ≥1.0.

Results:
During the study period, 144 patients were identified (mean age 13.7 ± 5.3 years). Among Current Era patients (n = 55), both older age at Fontan (R = 0.286,
p =
0.034) and Nakata index (R = 0.389,
p
= 0.049) were positively associated with %MVO
2
. There were negative associations between time from Fontan to EST (R = -0.367,
p
= 0.006) and Fontan pressure (R = -0.501,
p
= 0.015). For the entire cohort, longer time from Fontan to EST (R = -0.461,
p
< 0.001) and higher Fontan pressure (R = -0.271,
p
= 0.046) were associated with diminished performance. In both groups, multivariable regression was performed for variables that were significantly correlated (
p
< 0.05) with %MVO
2
. Time from Fontan to EST was significant for Current Era patients (slope coefficient -3.2, p = 0.010) and the entire cohort (slope coefficient -1.6,
p
= 0.005).

Conclusion:
Older age at Fontan after Glenn and shorter time from Fontan to EST are associated with higher %MVO
2
, suggesting that Fontan completion should be delayed in the current era. Smaller Nakata index and elevated Fontan pressure negatively correlate with %MVO
2
, providing a rationale for intervening on stenotic pulmonary arteries.
Abstract 9703: Lowering LDL Cholesterol, but not Raising LDL Receptor Activity, by Ezetimibe
Authors: Hayashi Hiroshi , Kawamura Mitsunobu
Published: April 2024

Introduction:
Ezetimibe, an inhibitor of intestinal cholesterol absorption, is effective in lowering serum low-density lipoprotein (LDL) cholesterol with or without co-administration of statin. Ezetimibe-plus-statin therapy enhances LDL receptor activity, but it is still unclear whether ezetimibe alone enhances LDL receptor activity resulting in LDL cholesterol decrease. Hypothesis: We assessed the hypothesis that ezetimibe lowers serum LDL cholesterol by raising LDL receptor activity in humans.

Methods:
Hypercholesterolemic patients (n = 28; age 61.3 ± 12.7 (mean ± SD); 57% male) were treated with ezetimibe (10 mg/day) for 4 months. Before and after the treatment, serum LDL cholesterol, high-density lipoprotein (HDL) cholesterol, and triglyceride were measured. Serum apolipoprotein A-I (apo A-I), B (apo B), and C-II (apo C-II) were also measured and the estimated LDL receptor activities were calculated by our previously reported methods as follows: LDL receptor activity (expressed as a percentage of normocholesterolemic subjects) = 63.6 + apo C-II (mg/dl) x 13.5 - apo B (mg/dl) x 0.37.

Results:
By the treatment of ezetimibe, LDL cholesterol (178.5 ± 26.2 vs. 141.1 ± 26.2 mg/dl, p < 0.01) was lowered 21% significantly and HDL cholesterol (56.1 ± 12.3 vs. 59.5 ± 16.2 mg/dl, p < 0.01) was increased 6% significantly. Triglyceride (184.4 ± 85.6 vs.174.8 ± 85.2 mg/dl, p = 0.60) was not changed. Serum apo B (136.2 ± 24.5 vs. 113.0 ± 23.8 mg/dl, p < 0.01) was lowered 17% significantly and apo A-I (143.5 ± 28.5 vs. 150.3 ± 31.9 mg/dl, p < 0.01) was increased 5% significantly. Apo C-II (5.9 ± 2.2 vs. 5.5 ± 2.2 mg/dl, p = 0.11) was not changed. The estimated LDL receptor activities before and after the ezetimibe treatment were 93.5 ± 25.1% and 96.9 ± 24.4%, respectively with no significant difference between them (p = 0.14).

Conclusions:
Ezetimibe lowered LDL cholesterol 21% significantly in hypercholesterolemic patients without raising LDL receptor activity. In conclusion, the enhancement of LDL receptor activity is suggested to be less involved in the pharmacological action of ezetimibe.
Abstract 9711: Cardioprotection by Endogenous Cardiac Myocyte P2x4; Receptors in Pressure Overload and Ischemic Heart Failure
Authors: Yang Tiehong , Shen Jian-Bing , Redden John , Yang Ronghua , Dodge-Kafka Kimberly , Liang Bruce T
Published: April 2024

Despite progress in its therapy, heart failure is a leading cause of mortality and morbidity. In defining a biological role of the ligand-gated ion channel P2X4 receptor, we uncovered a protective role of this channel in heart failure. P2X4 gene was flanked by loxP sites bwteen exons 2 and 4. The second loxP site together with the Frt-PGKneo-Frt cassette was inserted in intron 1 in a direction opposite to P2X4 transcription. After targeting the ES cells, PGKneo was removed by breeding chimeric males with ROSA26-Flpe females to generate

P2X4
flox/+

F1 pups. To create cardiac myocyte-specific knockout of P2X4 receptors, homozygous

P2X4
floxed/floxed

mice were bred with Tg mice (Myh6-cre/Esr1*, Jax stock no: 005650) containing a tamoxifen responsive Cre-estrogen receptor chimeric recombinase driven by the α-myosin heavy chain promoter. Knockout of P2X4 receptors (KO) was confirmed by lack of detectable P2X4 with immunoblotting and by lack of contractile response to the P2X agonist 2-methylthioATP. KO animals showed normal basal cardiac function but depressed contractile performance in both left coronary artery ligation and pressure overload models of heart failure by echocardiography and isolated working heart parameters. By contrast, cardiac myocyte-specific overexpression of the P2X4 receptor protected against pressure overload-induced and post-infarct heart failure. P2X4 receptors co-immunoprecipitated with nitric oxide synthase 3 (NOS3 or eNOS). Administration of eNOS inhibitor L-NIO blocked the salutary effect of cardiac P2X4 receptor overexpression in post-infarct heart failure as did eNOS knockout. The present study uncovered a protective role of endogenous cardiac myocyte P2X4 receptors in heart failure and demonstrated an important role of eNOS in mediating this protection.