bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 13147: The Prognostic Value of Coronary CTA in Young versus Older Patients Depends on the Outcome
Authors: Bittencourt Marcio , Hulten Edward , Gohshhajra Brian , Cheezum Michael , Hoffmann Udo , Abbara Suhny , Di Carli Marcelo , Lotufo Paulo A , Blankstein Ron
Published: April 2024

Introduction:
Considerable debate exists on the optimal outcome in cardiovascular (CV) prognostic studies, particularly across different age groups.

Objective:
We sought to compare the use of all-cause death and CV events (CV death or MI) among patients undergoing coronary computed tomography angiography (CCTA) across different age groups.

Methods:
We included all consecutive patients with no known coronary artery disease (CAD) referred for CCTA. Severity of CAD was categorized as non-obstructive (normal or <50% stenosis) in 1525 (77%) patients or obstructive (≥50% stenosis) in 717 (23% ) of the patients. Age was categorized as young (< 60 years-old) in 2008 (62%) patients or old (≥60 years old) in 1234 (38%). Blinded event adjudication was performed for all-cause death, CV death or myocardial infarction (MI).

Results:
Among 3242 patients (58% males, 56±13 years), 92 (2.8%) CV events and 144 (4.4%) all-cause deaths occurred over a median follow up of 3.6 years (IQ: 2.1 - 5.0). While the presence of obstructive CAD was equally associated with CV death or MI in younger and older individuals, the association between obstructive CAD and all-cause death was only significant for younger individuals both in the crude analysis and after adjustment for the pretest probability of disease (figure).

Conclusions:
While the association of CAD with CV events is equal for younger and older individuals, the association of CAD with all-cause death was attenuated by age in our study.These suggests that the use of all-cause death among older patients referred for coronary CTA may be less representative of cardiovascular events and it may attenuate potentially significant differences in patient outcomes.
Abstract 13280: Prevalence and Location of Cardiovascular Disease in Familial Hypercholesterolemia and Unaffected Relatives. SAFEHEART (Spanish Familial Hypercholesterolemia Longitudinal Cohort Study) Results
Authors: Saltijeral Cerezo Adriana , Perez de Isla Leopoldo , Alonso Rodrigo , de Andres Raimundo , Miramontes Pablo , Zambon Daniel , Sanchez Muñoz-Torrero Juan F , Padro Teresa , Almagro Fatima , Mata Pedro
Published: April 2024

Introduction:
Heterozygous familial hypercholesterolemia (HeFH) increases the risk of cardiovascular disease. Traditionally it has been reported that the most affected territory is the coronary arteries tree. However, there are very few data from large cohorts of HeFH and even fewer data comparing them with a control population.

Hypotesis:
To analyse the prevalence and location of cardiovascular disease in individuals with HeFH and their families with negative genetic diagnosis in a large study.

Methods:
Data from the study, which recruited 3745 individuals aged 18 and olderbetween January 2004 and November 2013 were analysed. Out of them, 2752 were genetically diagnosesof HeFH and 993 were family members without the mutation.

Results:
Median age of individuals with HeFH was 44 years (18-89) and 40 (18-87) in unaffected relatives. One thousand, two hundred and sixty four (45.90%) HeFH and 463 (46.60%) controls were male. Table and figure show atherothrombotic disease prevalence in different locations.

Conclusions:
The prevalence of atherothrombotic disease is higher in individuals with HeFH than in their unaffected relatives. In HeFH patients, the predominant involvement is at the level of the coronary tree.
Abstract 13325: Apoptogenic Protein is Involved in Endothelial Senescence Induced by High Glucose
Authors: Yasuda Osamu , Soejima Hirofumi , Miyata Keishi , Yasuda Hisayo , Oike Yuichi , Ogawa Hisao
Published: April 2024

Background:
The Apoptogenic protein (Apop) is a novel mitochondrial protein originally identified in the atherosclerotic smooth muscle cells cultured from thoracic aortas of ApoE-deficient mice. The production of Apop using an expression vector induces death of smooth muscle cells in culture, and the inhibition of the Apop gene using siRNA prevents the reduction of cell viability induced by death inducing molecules. However, the physiological functions of Apop and its implication in diseases remain to be elucidated. Herein, we show that Apop is involved in the mechanism of high glucose-induced ROS production and senescence in endothelial cells.

Methods and Results:
Apop gene siRNA was introduced into human umbilical vein endothelial cells (HUVECs) using cationic lipid reagent. High glucose induced ROS production in HUVECs. Apop gene inhibition by siRNA also induced ROS production from these cells; however, HUVECs cultured in the presence of high glucose did not produce higher levels of ROS after the introduction of Apop siRNA, suggesting that high glucose and Apop inhibition may induce ROS generation in a similar way. Cells cultured in the presence of high glucose produced higher levels of ATP than in normal glucose. As expected, Apop inhibition increased ATP production of HUVECs to a similar extent as did high glucose. Morphologically, mitochondrial fragmentation, which is considered to contribute to ROS overproduction because of high glucose, was observed in HUVECs by Apop inhibition, similar to as in high glucose treated cells. As in high glucose cells, Apop gene inhibition induced senescence of HUVEC as assessed by senescence-associated b-galactosidase expression. Moreover, the expression of endothelial nitric oxide synthase of HUVECs was reduced by the inhibition of Apop.

Conclusion:
These results suggest that the Apop gene is implicated in mitochondrial ROS generation enhanced by glucose, and in endothelial senescence, which play important roles in the development of atherosclerosis; therefore, Apop could be a novel therapeutic target for the prevention of atherosclerosis in diabetes mellitus patients.
Abstract 13355: Risk Factors and Prognostic Role of Left Atrial Enlargement in Patients With Light-chain Cardiac Amyloidosis
Authors: Zhao Lei , Tian Zhuang , Fang Quan
Published: April 2024

Introduction:
Cardiac AL amyloidosis carries a poor prognosis so early diagnosis is essential for effective disease-modifying therapy. Echocardiography is a non-invasive modality used for evaluating cardiac diastolic dysfunction, which appears to be a convenient examination. Left atrium (LA), a characteristic of diastolic feature, plays a role in modulating cardiovascular performance. As part of routine clinical examination, we adopted LA diameter indexed to body surface area (LADi) as the parameter to evaluating LA size. Therefore, we aimed to assess risk factors and prognostic values of LA size measured by a simple echocardiographic index in cardiac AL amyloidosis.

Methods:
A retrospective analysis of patients with biopsy-proven cardiac AL amyloidosis was conducted. LA enlargement was defined as LADi greater than 23mm/m
2
.

Results:
A total of 104 cardiac AL amyloidosis patients were included in the final analysis, 61(58.7%) of which showed a presentation of LA enlargement. 64.4% were males, mean age was 55 ± 12 y and 57.7% were accompanied with severe heart failure (HF) (NYHA III to IV). Age, NYHA, ejection fraction (EF) and early/late mitral velocity ratio (E/A ratio) were independently associated with LA enlargement in the univariate analysis. But after fitting a multivariate logistic model, NYHA and EF did not remain in the final analysis. During a mean follow-up period of 39 months, the overall survival was significantly shorter in the group with a larger LA (median 5 months vs 22 months, p<0.001). LA enlargement was related with all-cause mortality with a hazard ratio of 1.94 (95%CI: 1.14-3.29, p=0.015) and was also a risk factor of severe HF (hazard ratio 2.18, 95%CI: 1.12-4.23, p=0.022).

Conclusion:
In cardiac AL amyloidosis, age and E/A ratio were main independent risk factors regarding LA enlargement. LA enlargement, evaluated by LADi, seemed to be related to prevalence and incidence of severe HF and was also a significant predictor of mortality.
Abstract 13403: Vagal Nerve Stimulation Mitigates Aberrant Gut Flora Observed in Guinea Pigs With Pressure Overload
Authors: Campbell Regenia P , Duffourc Michelle , Schoborg Robert V , Beaumont Eric
Published: April 2024

Background:
Altered gut microbial diversity has been associated with several chronic disease states, including heart failure. The vagus nerve, which innervates the heart and abdominal organs, carries information bi-directionally along the gut/brain axis. We hypothesized that vagal nerve stimulation (VNS) could alter gut microbial flora and correct aberrations observed in fecal samples from heart failure animals.

Methods and Results:
A stimulating device was implanted on either the left or right vagus prior to creation of pressure overload (PO) by aortic constriction. Animals then received continuous, cycling stimulation or sham treatment, and their heart function was monitored by echocardiography. Left ventricular end systolic and diastolic volumes, stroke volume, and cardiac output were significantly impaired in PO animals compared to baseline. VNS mitigated these effects. Animals that did not improve with VNS (15%) were categorized as non-responders. The bacterial DNA 16s ribosomal RNA gene was amplified from fecal DNA and amplicons sequenced for identification of bacterial genera present. Thirty-seven genera were identified as representing at least 0.1% of the total microbial population. Of these, the presence of 17 was disrupted by induction of PO and attenuated by VNS (six with either left or right VNS, five with right VNS only, and six with left VNS only). Metatranscriptomics analysis was then used to predict functional pathways that may be affected by the changes in diversity indicated by sequencing. Genera that express genes associated with ATP-binding cassette (ABC) transport and amino sugar/nitrogen metabolism were significantly changed by PO and VNS therapy. PO-induced changes were mitigated by left cervical vagus stimulation and exacerbated in samples from animals that did not respond to treatment.

Conclusion:
These data suggest that VNS may improve heart function, at least in part, by reversing pathogenic changes in gut flora that result from blood pressure overload.
Abstract 13440: The Asp358 A/C Polymorphism in Interleukin-6 Receptor Gene as a Novel Predictor of Atrial Fibrillation Following Coronary Artery Bypass Graft Surgery in Chinese Han Population
Authors: Wu Fangqin , Ding Shu , Feng Xinwei , Yu Meng , Lu Sai , Zhao Haibo , Wu Ying
Published: April 2024

Objective:
Growing evidences suggest that genetic variation in inflammatory cytokines may play a key role in the development of postoperative atrial fibrillation (POAF). This study aimed to examine the association between three single-nucleotide polymorphisms in interleukin-6 receptor (IL-6R) gene Asp 358 A/C, IL-6 gene -174 G/C and -597 G/A and POAF following coronary artery bypass grafting (CABG).

Methods:
This prospective study enrolled 371 Chinese Han patients undergoing first time isolated CABG. The primary endpoint was the occurrence of POAF lasting ≥ 5mins. The patients were grouped as either POAF or non-POAF according to their ECGs, which were continuously monitored for the first 7 postoperative days. Genotypes for IL-6R gene Asp358 A/C, IL-6 gene -174 G/C and -597 G/A were determined. Multivariate logistic regression analysis was performed to identify independent risk factors for POAF.

Results:
Overall, 112 (30.2%) patients developed POAF. There was no significant difference in demographic and clinic data between the two groups, except that patients in the POAF group were significantly older than those in the non-POAF group (p < 0.001), patients who had POAF appeared to have cerebrovascular disease more frequently than those who did not have POAF(p < 0.05). Although frequencies of alleles and genotypes of IL-6 gene -174 G/C and -597 G/A polymorphism were similar in both groups, the CC genotype distribution and C allele frequencies of IL-6R gene Asp358 A/C were significantly higher in patients with POAF than those without POAF (p = 0.003). Univariate logistic analysis showed that the CC genotype for IL-6R gene Asp358 A/C, age, and history of cerebrovascular disease emerged as predictors of POAF. Multivariate analysis shows that the CC genotype for IL-6R gene Asp358 A/C and age were independent predictors of POAF. The adjusted (OR 2.06; 95% CI, 1.16 - 3.63; p = 0.01) of the CC genotype for IL-6R gene Asp358 A/C for predicting POAF was even greater than the unadjusted (OR 1.22; 95% CI, 1.01- 1.64; p = 0.04).

Conclusions:
This study suggests IL-6R gene Asp358 A/C polymorphism may contribute to the genetic susceptibility of POAF after CABG in Chinese Han population.
Abstract 13445: Thrombin-Inhibiting Nanoparticle Treatment Focally Reduces NF-kB Activation and Tissue Factor Expression in Atherosclerotic Plaques
Authors: Palekar Rohun U , Jallouk Andrew P , Pan Hua , Wickline Samuel A
Published: April 2024

Introduction:
Thrombin plays a significant role in atherogenesis through PAR-1 signaling on various cell types and downstream activation of NF-kB, a potent driver of inflammation and hypercoagulability via tissue factor (TF) production in plaques. Herein, we demonstrate the use of perfluorocarbon nanoparticles (NP) bound to the direct thrombin inhibitor D-phenylalanyl-L-prolyl-L-chloromethylketone (PPACK: 13650 per NP) for downregulation of NF-kB activity and inhibition of tissue factor (TF) production.

Methods and Results:
Cell surface TF expression was assessed in vitro using a functional assay of Xa generation on human aortic endothelial cells (HAECs) and THP-1 monocytes following a six hour incubation with 1 U/ml and 4 U/ml thrombin and either saline, free PPACK, control NP or PPACK NP. Treatment with PPACK NP in both cell types at the two thrombin concentrations completely suppressed excess surface tissue factor expression over baseline levels, in contrast to cells treated with saline or control NP. Thrombin’s ability to activate NF-kB in HAECs via degradation of the cytoplasmic regulatory complex IkB was fully inhibited by PPACK NP as well.

PPACK NP were evaluated in vivo in ApoE-/- mice fed a Western diet for a total of 4 months. The mice received 1 ml/kg saline, control NP or PPACK NP intravenously 3 times/week for the final month of feeding. Following treatment, aortas were sectioned for histological analysis of tissue factor expression and NF-kB activation. PPACK NP treatment resulted in a 25.95% decrease in plaque associated tissue factor (Figure, p = 0.027) and diminished phosphorylated-p65 staining compared to saline and control NP treatment. Clotting parameters and bleeding times normalized within 60 min of i.v. delivery of PPACK NP.

Conclusion:
Inhibition of thrombin and PAR-1 signaling with PPACK NP exhibits a sustained reduction in local NF-kB activation and tissue factor expression in atherosclerotic plaques without causing a bleeding diathesis.
Abstract 13470: RV Ejection Efficiency Measured in the Phasic Pulmonary Flow; a CMR Approach in PAH
Authors: Biederman Robert W , Doyle Mark , Rayarao Geetha , Thompson Diane , Yamrozik June , Williams Ronald B , Correa-Jaque Priscilla , Benza Raymond
Published: April 2024

Introduction:
Measurements of RV function, such as RVEF and RV-measured ventricular-vascular coupling (VVC), maybe important in predicting survival in PAH, but are dependent on load and mathematical assumptions. However, independent measures, such as flow efficiency (FEI) within the main PA may be better predictors. FEI is dependent on the natural ratio between MPA area to pulsatile blood wavelength (λ), where λ is proportional to the product of λ velocity and the pulse time, but is difficult to measure directly.

Hypothesis:
We hypothesize pulmonary FEI will correlate with the VVC and RVEF.

Methods:
CMR was performed on 18 pts with PAH to assess RV function. Eight pts additionally underwent RV CMR during physiologic stressors: 1) inhaled NO 2) dobutamine (20μ/kg/min) and 3) volume challenge (500ml NaCl). MPA flow was measured via phase velocity mapping (PVM). The RVEF, VVC ratio and ejection time (ET) were calculated from CMR. The MPA area was measured from the PVM images along with avg velocity (Vel
avg
. Pulmonary FEI = (average Vel
avg
x ET) / MPA area.

Results:
A total of 38 unique measures of RVEF (52±12%), VVC (0.89±.3) and MPA flow conditions were measured: Vel
avg
(49±15cm/s), MPA area (51±11mm
2
) and ET (295±61ms). The FEI correlated with RVEF and VVC via log term: RVEF = 11.5 log
nat
(FEI) + 37.2; and VVC = 0.34 log
nat
(FEI) + 1.17.Bland-Altman analysis of the measured RVEF vs. the FEI modeled RVEF (Fig 1) has an offset bias of 0, a four SD range of ±14.4; r=0. 0.8, while the measured VVC vs. modeled has a bias of 0 and a 4 SD range of ± 0.45; r = 0.74.

Conclusions:
The linear combination of average pulmonary blood velocity, ejection time and MPA area combine to form a pulmonary FEI that strongly correlates with RVEF and VVC. Importantly, it is
devoid
of the afterload/preload assumptions of RVEF and the multitude of assumptions of V
0
and RVEDP in VVC. As such, this index may provide additional clinical value since it reflects the directly measured intrinsic efficiency of integrated RV-PA conditions.
Abstract 13475: Acute Hemodynamic Effects of Large Capacity Intra-aortic Balloon Counterpulsation Pumps in Patients With Advanced Heart Failure
Authors: Buiten Lyanne , Paruchuri Vikram , Morine Kevin , O'Kelly Ryan , Pham Duc Thinh , Kiernan Michael , Shih Jeffrey , Kimmelstiel Carey , DeNofrio David , Karas Richard H , Kapur Navin K
Published: April 2024

Over 40,000 intra-aortic balloon counterpulsation pumps (IABPs) are implanted in the United States annually. We explored the hemodynamic effect of large capacity (50cc) IABPs in patients with advanced heart failure.

Methods:
We conducted a prospective, observational study in 10 consecutive patients with Stage D, NYHA Class 3 or 4, non-ischemic heart failure referred for non-emergent IABP placement. Left ventricular (LV) hemodynamics were recorded for 10 minutes using a conductance catheter (CD Leycom; Figure) before and after activation of a 50cc IABP (Maquet Inc). Next, the 50cc IABP was halted for 10 minutes and a 10cc gas-extension tube inserted into the driveline to reduce the displacement volume to 40cc. LV hemodynamics were again recorded for 10 minutes before and after 40cc-IABP activation.

Results:
Mean age of the study population was 58±14 with an LV ejection fraction of 15±8%. The 50cc IABP reduced LV stroke work (LVSW: 1666±760 vs 1260±774 mmHg x mL, p<0.01), end-systolic pressure (LVESP: 89±24 vs 75±23 mmHg, p<0.05), and dP/dt max (868±225 vs 744±220 mmHg/sec, p<0.01). The IABP with 40cc of volume displacement reduced LVSW (1717±814 vs 1424±703, p<0.05), LVESP (94±19 vs 84±20, p<0.05), and dP/dt max (890±171 vs 810±179, p<0.01). Both 50cc and 40cc settings increased aortic diastolic pressures and reduced systolic pressures to similar degrees. Neither 50cc nor 40cc of volume displacement altered arterial elastance, LV volumes, or end-diastolic pressures (Figure). No hemodynamic differences between 50cc and 40cc of volume displacement were observed.

Conclusions:
This is the first study of large capacity IABPs using conductance catheters in patients with advanced heart failure. Both 50cc and 40cc volume displacement balloons reduced LV stroke work primarily by reducing LV end-systolic pressure with minimal effect on LV volumes. The clinical utility of IABPs in heart failure requires further study.
Abstract 13502: Statins Buffer the Vasoconstricting, Pro-Inflammatory and Pro-Oxidant Effects of Experimental Venous Congestion in Patients With Systolic Heart Failure on Stable Medical Regimen
Authors: Colombo Paolo C , Wong Ka Yuk , Onat Duygu , Hayashi Yacki , Harxhi Ante , Ahmad Myra , Cremers Serge , Sabbah Hani N , Le Jemtel Thierry H , Demmer Ryan T
Published: April 2024

Background:
In heart failure (HF), statins decrease hospitalizations for acute decompensation, which are primarily due to venous congestion (VC). The reason is unknown. We tested whether statins buffer the vasoconstricting, pro-inflammatory and pro-oxidant effects of VC in an established human model of this condition.

Methods:
We studied 41 pts, NYHA class II-III, LVEF <40%, euvolemic and on stable medical therapy. To experimentally model VC, venous arm pressure was increased to 30 mmHg above baseline by inflating a pressure cuff around the dominant arm. Blood was sampled from test and control arm (lacking an inflated cuff) before and after 90 minutes of VC. Plasma endothelin-1 (ET-1), interleukin-6 (IL-6), and vascular cell adhesion molecule 1 (VCAM-1) were measured by ELISA; isoprostane by LC-MS.

Results:
Age was 53±2 years, 32% were female, 29% had an ischemic etiology, LVEF was 22±1%, 56% were treated with a statin. Experimental VC increased plasma isoprostane, ET-1, VCAM-1 and IL-6. However, the use of a statin greatly influenced the rate of this response: the increase in isoprostane (marker of oxidative stress) was four-fold higher among nonstatin vs statin users (62.3±11 vs 15.4±11.2 pg/ml, p=0.01); ET-1 (marker of vasoconstriction and inflammation) increased 50% more among nonstatin users (1.83±0.23 vs 1.21±0.21 pg/ml, p=0.05); VCAM-1 (marker of endothelial activation) increased 80% more among non-statin users (62.5±15.1 vs 33.6±13.3 pg/ml, p=0.16). Changes in IL-6 (marker of inflammation) did not differ in the two groups (1.2±.08 vs 1.1±0.08 pg/ml, p=0.78). Of note, the effects of statins on ET-1 was dose-dependent. Conclusions: We provide the first evidence that statins (particularly at high dose) partially buffer the vasoconstricting, pro-inflammatory and pro-oxidant effects of experimental VC. Future studies are warranted to address whether short-term high dose statins have an adjunctive role in the treatment of acute decompensation in HF pts.
Abstract 13533: Impact of Cola Drinking on the Cardiorenal Axis in Rats
Authors: Otero-Losada Matilde , Gómez Llambí Hernán , Müller Angélica , Ottaviano Graciela , Cao Gabriel , Ambrosio Giuseppe , Milei José
Published: April 2024

Introduction.
The cardiorenal syndrome is a constellation of interactive cardiac and renal risk factors. We reported that chronic cola drinking induces metabolic syndrome and pro-oxidative metabolism in rats.

Hypothesis
. To evaluate whether chronic cola drinking affects cardiorenal integrity in relation with oxidative metabolism and local inflammation in rats.

Methods.
Male Wistar rats drank ad libitum regular cola (C, n=12) or water (W, n=12). Measures/recordings: body weight (weekly), nutritional data (twice a week); at 0 mo and 6 mo: plasma glucose, cholesterol fractions, TG, uric acid, creatinine (enzymocolorimetry), coenzyme Q-10 (RP-HPLC-ED), SBP (plethysmography), echocardiograms (awake rats). At 6 mo euthanasia was performed. The heart and kidneys were excised and processed for histopathology and immunohistochemical IL-6 and TNFα staining. Glomerulosclerosis and histopathology score were semiquantitatively evaluated. ANOVA, Bonferroni t-test, Pearson r, p<0.05 significant.

Results.
Compared with W, C rats showed: I). overweight (8%, p<0.05), hyperglycemia (11%, p<0.05), hypertriglyceridemia (2-fold, p<0.001), higher atherogenic index in plasma (2-fold, p<0.01), lower Q
10
levels (-55%, p<0.05); II). higher LV diastolic diameter (+9%, p<0.05) and volumes (diastolic 26%, p<0.01; systolic 24%, p<0.05), posterior wall thinning (-8%, p<0.05) and larger cardiac output (24%, p<0.05); III). glomerulosclerosis (21%, p<0.05), higher histopathological score (13%, p<0.05), IL-6 (7-fold, p<0.001) and TNFα (4-fold, p<0.001) expression; IV). Left ventricle dimensions were strongly correlated with IL-6 (74%, r=0.86, p<0.001) and TNFα (52%, r=0.72, p<0.001). Controlling for either or both TG and Q
10
reduced the strength of correlations or nearly abolished them.

Conclusions
. Cardiac remodeling was associated with increased pro-inflammatory cytokines and renal damage. Cardiorenal association was highly dependent on hypertriglyceridemia and Q10 level. Hypertriglyceridemic lipotoxicity in a context of defective antioxidant and anti-inflammatory protection due to low Q10 level might be involved in the cardiorenal syndrome induced by chronic cola drinking in rats.
Abstract 13542: Psychosocial Predictors of Duration of Obesity: The Coronary Artery Risk Development in Young Adults (CARDIA) Study
Authors: Cooper-McCann Rebecca , Reis Jared , Loria Catherine , Lewis Cora E , Ayers Colby , Diez-Roux Ana , Powell-Wiley Tiffany M
Published: April 2024

Introduction:
Cumulative exposure to excess adiposity contributes significantly to cardiovascular morbidity and mortality. However, little is known about associations of psychosocial factors [life events (LE) and social support (SS)] with duration of abdominal obesity (DOB).

Methods:
Baseline data were collected in CARDIA from 1985-1986 (N=5115). Participants completed an 11-item SS scale, from Seeman’s and Syme’s work (higher score=higher support), and a 66-item LE scale, from the Psychiatric Epidemiology Rating Interview (higher score=more stressful events exposure in prior year). Associations between baseline SS and LE and DOB were investigated using multivariable linear regression. Abdominal obesity was waist circumference (WC)>102cm for men and >88cm for women. DOB was defined as cumulative abdominal obesity years based on measured WC every 3-5 years in the 25-year study.

Results:
Among 4214 participants not initially obese, DOB ranged from 0-25 years with a median of 10 years/person. At baseline, those with high LE scores were younger, more likely to be black, with less education, greater total physical activity (PA), greater energy intake (EI) and current/past smoking, while those with high SS score were more likely to be female, black, with higher education, higher PA, lower EI and smoking. In stratified linear regression models adjusted for covariates, each 1-unit higher LE score was associated with longer DOB for white women (Table). In contrast, a 1-unit higher SS score was associated with shorter DOB for white women and white men. No associations were observed among black men or women.

Conclusions:
Psychosocial factors were associated with duration of abdominal obesity, with a positive association between LE score and DOB for white women, and an inverse association between SS score and DOB for white women and men. These factors may identify those most at risk for greater cumulative exposure to adiposity and may serve as obesity prevention targets.
Abstract 13561: The Emerging Role of Stress Speckle Tracking in Viability World
Authors: Saleh Ahmed M , Zintl Konstantin , Brachmann Johannes
Published: April 2024

Introduction:
Speckle-tracking echocardiography has recently emerged as a quantitative ultrasound technique for accurately evaluating myocardial function by analyzing the motion of speckles identified. Speckle-tracking obtained under stress may offer an opportunity to improve the detection of dynamic regional abnormalities and myocardial viability.

Objective:
To evaluate stress speckle tracking as tool to detect myocardial viability in comparison to cardiac MRI in post-STEMI patients.

Methods:
71 patients were prospectively enrolled in our 18-month’s study. Dobutamin stress echocardiography was performed 4 days post-infaction accompanied with automated functional imaging (Speckle tracking) analysis of left ventricle during rest and then during low dose stress. All patients underwent a follow up stress echocardiography at 6 weeks with speckle tracking analysis. Cardiac MRI took place concomitantly at 4 days post-infarction and 6 weeks. We carried out an assessment of re-admission with acute coronary syndrome (ACS) after one year of enrollment.

Results:
Investigating strain rate obtained with stress speckle tracking after revascularization predicted the extent of myocardial scar, determined by contrast-enhanced magnetic resonance imaging. A good correlation was found between the global strain and total infarct size (R 0.75, p< 0.001). Furthermore, a clear inverse relationship was found between the segmental strain and the transmural extent of infarction in each segment. ( R -0.69, p<0.01). Meanwhile it provided 81.82% sensitivity and 82.6% specificity to detect transmural from non-transmural infaction at a cut-off value of -10.15. Global stress strain rate showed 80% sensitivity and 77.5% specificity at a cut-off value of -9.1 to predict hospital re-admission with ACS. A cut-off value of -8.4 had shown a 69.23% sensitivity and 73.5% specificity to predict the re-admission related to other cardiac symptoms .

Conclusion:
Strain rate obtained from speckle tracking during stress is a novel method of detecting myocardial viability after STEMI .Moreover it carries a promising role in post-myocardial infarction risk stratification with a reasonable prediction of reversible cardiac-related hospital re-admission.
Abstract 13586: Early Initiation of Oral Intake in Adult Patients After Cardiothoracic Surgery is Safe and Reduces Thirst: Results of a Randomized Clinical Trial
Authors: Ford Catherine , McCormick Donna , Teng Wei , Parkosewich Janet
Published: April 2024

Aim:
Tradition-based care dictates that patients fast for several hours post-cardiothoracic (CT) surgery due to concerns for adverse events (nausea, vomiting, dysphagia, aspiration pneumonia), although evidence is lacking to support this practice. Prolonged fasting causes patients significant distress from thirst. Our aim was to determine the effect of an early liberal regimen of ice chips and water on adverse events and thirst after CT surgery. We hypothesized that a liberal regimen vs. usual care (UC) would not increase adverse events and would reduce thirst. Method: We used a randomized controlled trial design with a sample of 149 patients from an 18-bed CTICU. Written informed consent was obtained and patients were randomized to UC (6-hour fast post-extubation) or liberal regimen during the pre-operative visit. After fasting 1 hour post-extubation, patients in the liberal regimen were first assessed with a 6-item protocol for oral intake readiness, and then offered ice chips. An hour later, they were advanced to water.

Results:
The mean age was 66±12.4 years; 73.8% were male; 91.3% had coronary artery and/or valve surgery. The two groups were equivalent except for the post-operative mean dose of ketorolac that was higher in the UC group (p=.04). The table below shows no differences in nausea, vomiting, or dysphagia between the UC vs. liberal group, and no aspiration pneumonia. Complaints of high thirst levels 6 hours after extubation were greater in the UC group. In analysis adjusted for relevant demographic and clinical variables (logistic regression), patients in the liberal group were less likely to report high thirst levels, compared with UC patients (B=-.299, OR=.273, 95% CI .118-.630).

Conclusion:
Early initiation of ice chips and water post-extubation after CT surgery was not associated with adverse events, but was associated with significantly less thirst. In appropriate patients, early oral intake can reduce thirst, a distressing symptom.
Abstract 13608: Center Variation in Home Time Following Acute Ischemic Stroke
Authors: O’Brien Emily C , Xian Ying , Wu Jingjing , Saver Jeffrey L , Smith Eric E , Schwamm Lee H , Peterson Eric D , Reeves Mathew J , Bhatt Deepak L , Prvu-Bettger Janet , Hannah Deidre , Maisch Lesley , Lindholm Brianna , Hernandez Adrian F , Fonarow Gregg C
Published: April 2024

Background:
Stroke survivors have identified that home time is a high priority outcome, but there are limited data on factors associated with time at home following stroke as well as the degree to which home time varies among discharging hospitals.

Methods:
PROSPER is a PCORI-funded program designed with stroke survivors to evaluate post-stroke therapies and outcomes. We linked data for patients >65 years old who were enrolled in the GWTG-Stroke Registry to Medicare claims to ascertain home time, defined as time spent alive and out of a hospital or skilled nursing facility, at 90 days and 1 year after discharge for ischemic stroke. We used generalized mixed models with random effects to estimate adjusted mean home time for each hospital, accounting for patient characteristics. We then used linear regression to assess hospital factors associated with risk-adjusted home time.

Results:
From 2007-2011, 156,869 ischemic stroke patients at 1417 hospitals were linked to Medicare claims. Home time varied among hospitals, with overall unadjusted median home time (IQR) of 59.5 days (55.7-63.2) over the first 90 days and 270 days (256.0-281.1) over the first year. Hospital factors associated with more home time over 90 days included higher annual stroke volume; South, West, or Midwest geographic regions (vs. Northeast); and rural location (Table). Similar patterns were observed at 1 year. Compared with patients in the highest hospital home time quartile, patients in the lowest were older, more likely to be female, had more comorbidities, and had more severe strokes by NIHSS. Home time variation decreased after adjustment, with a median of 59.3 days (57.4-61.4) over 90 days and 270 days (266.3-274.2) over 1 year.

Conclusions:
In a population of older ischemic stroke survivors, home time after discharge varies by hospital stroke volume, severity case mix, and region. In adjusted analyses, hospital stroke volume and rural location were associated with more days at home following stroke.
Abstract 13613: 4D Echo-Derived Global Area Strain is a Better Mechanical Index of RV Function
Authors: Amacher Kacie , Zhu Meihua , Ashraf Muhammad , Sahn David J
Published: April 2024

Introduction:
There is increasing interest in image based evaluation of RV mechanics.

Hypothesis:
Four-dimensional echocardiography (4DE) accurately assesses RV function, compared against sonomicrometry.

Methods:
Six porcine RV models were studied. Each RV was connected to a pump apparatus to generate pulsatile motion. Six sonomicrometry (sono) crystals were sutured in a triangle formation onto the RV to acquire volume. Right ventricular ejection fraction (RVEF), 3D global area strain (GAS), global circumferential strain (GCS), global longitudinal strain (GLS), and global radial strain (GRS) were obtained by 4D echocardiography at stroke volumes of 30-70 ml. Results were correlated with RVEF determined by sonomicrometry analysis.

Results:
Linear regression of all EchoPAC-derived parameters, RVEF, GAS, GCS, GLS, and GRS showed strong correlations with RVEF from sono data (r = 0.73, r = 0.78, r = 0.72, r = 0.75, r = 0.75, respectively; all P < 0.001). Bland-Altman analyses showed a slight over-estimation of echo-derived 3D RVEF and strain when compared to sono-derived EF, but more than 95% of data points were within the limits of agreement.

Conclusions:
4DE demonstrates the ability to accurately and feasibly assess RV function, and GAS showed the highest correlation with the reference ejection fraction.
Abstract 13704: Leisure Activity is Associated With Prognosis in Heart Failure With Preserved Ejection Fraction - Results From the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial
Authors: Hegde Sheila M , Shah Amil M , Claggett Brian , Anand Inder S , Shah Sanjiv J , Sweitzer Nancy K , Pfeffer Marc A , Solomon Scott D
Published: April 2024

Background:
Leisure-time physical activity is inversely associated with cardiovascular (CV) outcomes in healthy populations but the impact of leisure activity in heart failure with preserved ejection fraction (HFpEF) is unknown. We hypothesized that poor leisure activity predicts CV outcomes in HFpEF patients.

Methods:
The baseline self-reported physical activities of 1751 subjects from the Americas region of the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial were categorized as poor, intermediate, or ideal by American Heart Association (AHA) criteria. Leisure activity was related to the primary composite outcome (heart failure [HF] hospitalization, CV mortality, or aborted cardiac arrest), its components, and all-cause mortality using multivariable Cox models.

Results:
The mean age was 71.5 ± 9.7 years. Few patients met AHA criteria for ideal activity (11.0% ideal, 14.0% intermediate, 74.9% poor). Over a median follow-up of 2.4 years, the primary composite outcome occurred in 519 patients with a total of 397 HF hospitalizations, 222 CV deaths, and 6 aborted cardiac arrests. Compared to those with ideal activity, poor baseline activity was associated with a greater risk of the primary outcome (HR 1.53; 95% CI, 1.10-2.13), HF hospitalization (HR 1.65; CI, 1.12-2.44) (Figure), CV mortality (HR 1.38; CI, 0.86-2.23), and all-cause mortality (HR 1.70; CI, 1.16-2.50) after multivariable adjustment for potential confounders. A dose-response relationship was also present such that those with the least activity demonstrated highest risk of the primary composite outcome, HF hospitalization, and all-cause mortality (p for trend all ≤ 0.01).

Conclusions:
In patients with HFpEF, poor baseline leisure activity is associated with higher risk of HF hospitalization and mortality.
Abstract 13716: Pharmacokinetics of Pravastatin in Pediatric Dyslipidemia Patients: Clinical Impact of Genetic Variation on Statin Disposition
Authors: Wagner Jonathan , Abdel-Rahman Susan , van Haandel Leon , Raghuveer Geetha , Kauffman Ralph , Leeder J. Steven
Published: April 2024

Background:
In adults, genetic variation of the drug transporter, organic anion transporting polypeptide (OATP1B1) encoded by the gene SLCO1B1, decreases hepatic uptake of statins. This leads to increased circulating statin concentrations in plasma, thereby placing patients at higher risk for adverse events and decreased efficacy. Expression of OATP transporters in mice changes during development, raising the question of whether in humans the genotype-phenotype relationship observed in adults is relevant in the developing child.

Methods:
Participants (8-21 years) with at least one allelic variant of SLCO1B1 c.521 T>C (521TC; n=8) and wild type controls (521TT; n=5) were enrolled in a single oral dose pharmacokinetics (PK) study. Pravastatin and isomers were quantified by liquid chromatography tandem mass spectrometry. A model-independent PK approach was used to define the peak plasma concentration (Cmax), area under the curve (AUC) during the sample period and AUC to infinity.

Results:
521TC subjects had a nearly 3-fold increase in Cmax (177.62 vs. 56.53 ng/ml; p=0.001) and AUC (389.81 vs. 139.57 ng/ml*h; p=0.004) compared to 521TT controls (Fig. 1). Formation of the 3-alpha-iso-pravastatin acid and lactone isomers in the acidic environment of the stomach prior to absorption was variable in both groups. There was a linear relationship between pravastatin acid AUC and the ratio of pravastatin acid to total analyte (pravastatin acid, 3-alpha-iso-pravastatin, and corresponding lactones) AUC amongst genetic variants (R=0.8961) that does not appear to be present in the control.

Conclusion:
The impact of the SLCO1B1 c.521 gene variant on pravastatin PK in adults was replicated in our pediatric cohort. However, other physicochemical factors appear to contribute to variability in the dose-exposure relationship. This data must be replicated in a larger cohort, and the pharmacodynamic consequences assessed, before implementing OATP1B1 driven dosing guidelines.
Abstract 13720: Mitral Valve Prolapse And Sudden Death: A Systematic Review
Authors: Nalliah Chrishan J , Mahajan Rajiv , Haqqani Haris , Lau Dennis H , Vohra Jitendra , Morton Joseph B , Kalman Jonathan M , Sanders Prashanthan
Published: April 2024

Introduction:
Mitral valve prolapse (MVP) is commonly observed as a benign finding in the general population. There is a suggestion from the literature that MVP is associated with unexplained sudden cardiac death (SCD) in patients with otherwise “structurally normal hearts”.

Aim:
We performed a systematic review 1) to determine the prevalence of MVP in unexplained SCD cohorts, 2) to determine the presence of MVP in the general population and 3) to evaluate the incidence of SCD in patients with MVP.

Methods:
An electronic search of the English medical literature (Pubmed, Medline, Cochrane and EMBase) was conducted on 1st July 2014. 667 references were imported into Endnote and reviewed. Reference lists of relevant studies and review articles were screened to retrieve non-indexed articles. All patients with known precipitants for death or cardiac arrest were excluded. 20 studies were identified with 13 examining MVP in unexplained SCD and 7 examining SCD in patients with MVP. A random effects model was utilized and meta-analysis was performed using STATA version 13.0.

Results:
The cause for SCD was not identified in 28.3% of autopsy studies. The prevalence of MVP in cohorts with unexplained SCD was 13.3% (95% CI 6.8, 21.3). The community prevalence of MVP was 1.6% (95% CI 1, 2.8) and the incidence of unexplained SCD in the MVP population was 0.2% (0.1, 0.3) per year. Based on current census data, we project that MVP presently affects approximately 5.1 million people in the United States and is estimated to climb to 6.3 million by 2050. Accordingly, the number of SCD victims with MVP will climb from 10, 200 to 12, 600. Bileaflet prolapse, moderate to severe mitral regurgitation, ventricular fibrosis and ventricular ectopy were observed more commonly in patients with unexplained SCD and MVP.

Conclusion:
The prevalence of MVP in victims of unexplained SCD is high. Although the incidence of life threatening arrhythmic events in the general MVP population remains low, the absolute number of people exposed to the risk of SCD will be large given the high prevalence of MVP. Further work is required to delineate potential risk factors for sudden death in patients with MVP.
Abstract 13724: Intravascular Ultrasound and Angiographic Predictors for 5-Year Target Lesion Revascularization After Second Generation Drug-Eluting Stent Implantation
Authors: Kitahara Hideki , Sakamoto Kenji , Okada Kozo , Kobayashi Yuhei , Kimura Takumi , Yock Paul G , Yeung Alan C , Fitzgerald Peter J , Honda Yasuhiro
Published: April 2024

Background:
Late target lesion revascularization (TLR) remains an unresolved problem in drug-eluting stents (DES). This study aimed to evaluate whether angiography and IVUS at mid-term can predict late-TLR in lesions treated with 2nd generation DES.

Methods:
Clinical outcomes were followed for 5 years in 1265 lesions with no TLR within the 1st year after Endeavor zotarolimus- (E-ZES, n=748), Resolute zotarolimus- (R-ZES, n=195), and everolimus-eluting stent (EES, n=322) implantation. Quantitative coronary angiography (QCA) and IVUS were performed at baseline and mid-term (8-12 months) follow-up.

Results:
During 1 to 5 years, R-ZES and EES showed equivalent late-TLR rates, while E-ZES demonstrated significantly less late-TLR than other stents (4.6%, 4.3% and 1.5%, respectively. Log Rank p=0.002). In E-ZES, no QCA or IVUS variables predicted late-TLR. In contrast, the late-TLR group in R-ZES and EES had smaller minimum lumen diameter (MLD), greater neointima and more late-acquired incomplete stent apposition (LISA) at mid-term follow-up, as well as greater increases of vessel and peri-stent plaque volumes during the follow-up. Multiple logistic regression analysis determined follow-up MLD, LISA and the increase of peri-stent plaque at mid-term as independent predictors of late-TLR in R-ZES and EES. In particular, with ROC-determined cutoff values, lesions with ≥2 predictors had a relative risk of 14.4 for late-TLR.

Conclusion:
The incidence and determinants of late-TLR can vary depending on the drug, carrier and release kinetics. Despite a trend for more TLR within the 1st year, E-ZES with phosphorylcholine coating was associated with an extremely low incidence of late-TLR and stable vessel response surrounding the stent. R-ZES and EES with durable polymer and longer release kinetics showed similar rates of late-TLR, possibly related to pathological responses of the stented artery that may be detectable by IVUS within the 1st year after implantation.
Abstract 13764: Development of
in vitro
Drug-Induced Cardiotoxicity Assay by Using Three-Dimensional Cardiac Tissues Derived From Human Induced Pluripotent Stem Cells
Authors: Takeda Maki , Miyagawa Shigeru , Fukushima Satsuki , Saito Atsuhiro , Ito Emiko , Matsuura Ryohei , Harada Akima , Oda Noriko , Amano Yuto , Matsusaki Michiya , Akashi Mitsuru
Published: April 2024

Introduction:
In vitro drug-induced cardiotoxicity assay is a critical step in drug discovery for clinical use. Use of induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is promising for this purpose; however, dissociated single iPSC-CMs are concerned by their functionality, while generation of artificial cardiac tissue by iPSC-CMs mimicking native cardiac tissue has not been established for the cardiotoxicity assay. We hypothesized that three-dimensional (3D) cardiac tissues derived from human iPSC-CMs (3D-hiPSC-CMs) may be used for in vitro drug-induced cardiotoxicity assay.

Methods and Results:
Single hiPSC-CMs coated with fibronectin and gelatin nanofilms were cultured in a cell culture insert to generate 3D-hiPSC-CMs. Histologically, the 3D-hiPSC-CMs formed thick multilayers dependent upon the number of seeded cells. In addition, the 3D-hiPSC-CMs exhibited sarcomere structure in the myocytes and extracellular matrix proteins, such as fibronectin, laminins or collagen type I/III. Electrophysiologically, synchronous extracellular electrical potentials were recorded in the entire 3D-hiPSC-CMs. Addition of cytotoxic doxorubicin at 2 uM induced release of lactate dehydrogenase (LDH), while that at 1 uM induced reduction of cell viability as assessed by WST assay. In contrast, addition of E-4031, hERG type potassium channel blocker, failed to induce cytotoxicity in the 3D-hiPSC-CMs by LDH and WST assay. Instead, E-4031 at 30 nM induced significant decrease in peak Ca2+ transient (80±4 vs 61±10 /min), beating rate (81±4 vs 77±7 /min), contraction velocity (9.2±1.9 vs 6.7±1.9 um/sec) and relaxation velocity (7.8±1.5 vs 3.3±0.8 um/sec). On the other hand, addition of Isoproterenol at 100 nM induced significant increase in peak Ca2+ transient (80±4.1 vs 96±8.0 /min), and beating rate (81±4.0 vs 115±11 /min), but failed to induce significant increase in contraction velocity (9.2±1.9 vs 11.4±1.4 um/sec) or relaxation velocity (7.8±1.5 vs 11±0.6 um/sec).

Conclusions:
The 3D-hiPSC-CMs exhibited doxorubicin-sensitive cytotoxicity and hERG channel blocker/isoproterenol-sensitive electrical activity in vitro, indicating its usefulness for drug-induced cardiotoxicity assay or drug screening system for drug discovery.