bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 12957: Prognostic Significance of Elevated Troponin I After Valve Heart Surgery
Authors: Aragao Roberto C , Sampaio Roney O , Bittencourt Marcio S , Lopes Antonio S , Accorsi Tarso A , Rosa Vitor E , Fernandes João R , Spina Guilherme S , Hajjar Ludhmila A , Tarasoutchi Flavio
Published: April 2024

Background:
Cardiac troponin is associated with adverse events after cardiac surgery. However, the ideal time for its measurement after surgery is unclear. In order to predict its relationship to in-hospital mortality, independent value of troponin I levels, at different time points during the first 72 hours after valvular heart surgery, was evaluated.

Methods:
All patients, who underwent valvular heart surgery at a single tertiary center from 2011 to 2015, were included. Troponin levels were grouped according to the time after surgery as: within the first 12h, 12 to 24h, 24 to 48h, and 48h to 72h. Univariable and multivariable logistic regression models were built to define the role of troponin measurements during the first 72 hours after surgery as predictors of in hospital mortality. The multivariable models were adjusted for EuroSCORE (ES). Model discrimination was compared using the area under the ROC curve.

Results:
1854 patients were included (48% women, mean age 56±15 years), with a mean ES of 4.5±3.6. The mortality was 14% (267 patients). Individuals who died during the admission had higher troponin values during the first 72 hours (p<0.001), the largest difference occurred after 24 hours (figure, left panel). After adjustment for the ES, all troponin measurements remained significantly associated with mortality (OR per 10 unit change in troponin: 1.3 before 12h; 1.4 at 12 to 24 hours, 1.8 at 24 to 48 hours; and 2.0 at 48 to 72 hours (p<0.001 for all). While initial post-operative troponin measurement did not significantly improved the discrimination for mortality (p=0.17 for troponin before 12 hours), the discrimination improved for late troponin measurements (figure, right panel).

Conclusion:
Postoperative troponin is independently associated with in-hospital mortality in individuals who underwent valvular heart surgery. Among the troponin values, those collected after 24 hours are more accurate independent preditors of in-hospital mortality.
Abstract 13135: Association of Three-Dimensional Tricuspid Valve Deformation With Functional Tricuspid Regurgitation
Authors: Ryo Keiko , Tanaka Hidekazu , Dokuni Kumiko , Hatani Yutaka , Matsuzoe Hiroki , Hatazawa Keiko , Shimoura Hiroyuki , Sano Hiroyuki , Sawa Takuma , Mochizuki Yasuhide , Motoji Yoshiki , Tatsumi Kazuhiro , Matsumoto Kensuke , Hirata Ken-ichi
Published: April 2024

Introduction:
Background: Functional tricuspid regurgitation (FTR) is widely recognized as being associated with poor outcomes in patients with various cardiac diseases, and the tricuspid valve (TV) deformation is an important mechanism of FTR. However, the precise assessment of TV deformation by means of two-dimensional echocardiography is limited.

Purpose:
The purpose of this study was thus to investigate the association of TV deformation with FTR by using three-dimensional transthoracic echocardiography (3D-TTE).

Methods:
We studied 65 patients with FTR. Their mean age was 60±16 years and 36 patients (55%) were female. FTR was quantified by the ratio of the jet area and corresponding RA area, and more than moderate FTR was defined as significant. 3D-TTE was performed to analyze the tricuspid deformation. Tricuspid tenting height and area were analyzed at the time of maximal systolic closure. TV area index, anterior-posterior (A-P) and septal-lateral (S-L) TV annular diameters were analyzed at end-diastole. Right ventricular longitudinal length, end-diastolic and end-systolic area index (EDAI, ESAI) and right atrial area index (RAA) were also obtained from 3D data set.

Results:
Twenty-one patients were classified as having significant FTR. Tenting height (6.5±3.1 vs. 4.0±1.8 mm, p<0.001), tenting area (1.3±0.8 vs. 0.7±0.4 cm2, p=0.003), TV area (6.9±1.7 vs. 5.0±1.4 cm2/m2, p<0.001) and S-L (35±4 vs. 28±6 mm, p<0.001) in patients with FTR were significantly larger than those in patients with non-significant FTR, but A-L was not (38±6 vs. 36±7mm). After adjusting for age, ESAI, RAA and tenting height, a multivariate logistic regression analysis showed that TV area (odds ratio 3.1, p=0.04) was independently associated with significant FTR.

Conclusions:
TV-related parameters were associated with FTR, and TV area was the most important factor for FTR. Our findings by means of 3D-TTE may well have clinical implications for better management of patients with FTR.
Abstract 13154: Modulation of Stem Cell Niche and Stem Cell Migration Promotes Functional Angiogenesis by Enhancing Stem Cell Homing in Ischemic Rat Myocardium: A Novel Concept of Cell-free Regeneration Therapy
Authors: Sougawa Nagako , Miyagawa Shigeru , Fukushima Satsuki , Saito Atsuhiro , Masuda Shigeo , Harada Akima , Imanishi Yukiko , Sato-Nishiuchi Ryoko , Sekiguchi Kiyotoshi , Sawa Yoshiki
Published: April 2024

Background:
The microenvironments composed of extracellular matrix (ECM) components and cytokines are considered to be involved in the decision of the stem cell fate and behavior. In addition, some cytokines induced by ONO1301 has been reported to enhance cell migration contributing to myocardial regeneration. In this study, we hypothesized that combined administration of cardiac specific ECM such as laminins and ONO1301 may enhance regeneration process by modulation of stem cell activity and homing.

Methods and Results:
In vitro study revealed that MSCs showed strong adhesion to laminin (LM) 511. ONO1301 promoted the production of several cytokines in smooth muscle cells, and it enhanced MSCs migration in vitro assay. To examine the therapeutic effect of ONO1301 combined with LM511, we transplanted ONO1301 or ONO1301 with LM511 (n=5-12) in a rat acute myocardial infarction model. Four weeks later, the number of PDGFRα- and CD90-positive cells tended to be higher in the combination (ONO1301 with LM511) group than in the ONO1301 alone group. Furthermore the gene expression of Sca-1 and c-kit was higher in the combination group than the control group (Sca-1, ONO1301 with LM511: 2.16- (p<0.05), ONO1301 alone: 2.01-fold to the control, c-kit, ONO1301 with LM511: 2.75- (p<0.05), ONO1301 alone: 1.45-fold to the control). Histological examination revealed that the number of ILB4 (endothelial cell marker) positive cells was significantly higher in the combination group than in the ONO1301 group (ONO1301 with LM511: 521±68 cells/mm
2
, ONO1301 alone: 281±10 cells/mm
2
, control: 195±29 cells/mm
2
; p<0.05). Moreover, the number of CD31 (endothelial cell marker) and SMA (smooth muscle cell marker) double positive cell was significantly higher in the combination group compared with the control group (ONO1301 with LM511: 616±44 cells/mm
2
, control: 226±60 cells/mm
2
; p<0.05). Real time PCR analysis revealed that SDF-1, PGF, FGF2 and HGF were higher in the combination group. Moreover, infarct size tended to be smaller in the combination group than in the ONO1301 group.

Conclusion:
The cell free regeneration therapy using both ONO1301 and LM511 may contribute to enhanced stem cell homing to implanted site, leading to improve functional angiogenesis in rat ischemic heart.
Abstract 13246: The Role of Kca3.1 in Monocyte-macrophage Polarization and Its Relevance to Atherosclerotic Plaque Instability
Authors: Xu Rende , Li Chenguang , Qian Juying , Ge Junbo
Published: April 2024

Background
Emerging evidence indicates that pro-inflammatory monocyte-macrophage polarization imbalance play key role in the atherosclerotic plaque progression and instability. The calcium-activated potassium channel KCa3.1 is critically involved in macrophage activation and function. However, the role of KCa3.1 in transcriptional regulation of monocyte-macrophage polarization and its relation to plaque instability is still unknown.

Methods
THP-1 monocytes were differentiated into macrophages using phorbol myristate acetate (PMA) and polarized into M1 by IFN-γ and LPS and into M2 macrophages by IL-4. Monocytes/macrophages were treated with KCa3.1 blocker TRAM-34 during differentiation or polarization. Animal model of plaque instability was induced by combined partial ligation of the left renal artery and left common carotid artery in apolipoprotein E knockout mice. From 6 weeks after surgery, the animals were treated with subcutaneous injection of TRAM-34 (120 mg/kg/d), or vehicle (miglyol 812) for 4 weeks. Phenotypic markers of macrophages and histological plaque characteristics were analysed.

Results
Significant up-regulation of KCa3.1 expression was found during the differentiation of THP-1 monocytes to macrophages. TRAM-34 treatment reduced the polarization of THP-1-derived macrophages to proinflammatory M1 macrophage while increasing the polarization of THP-1-derived macrophages to anti-inflammatory M2 macrophages. Further mechanistic studies indicated that KCa3.1 blocker promoted an M2 macrophage phenotype through up-regulation the activation of PPAR-γ. In animal models, KCa3.1 blockade therapy with TRAM-34 strikingly reduced the incidence of plaque rupture and luminal thrombus in carotid arteries. Moreover, macrophages within atherosclerotic lesions of mice receiving TRAM-34 injection showed decreased expression of markers associated with M1 macrophage polarization and enhanced expression of the M2 markers.

Conclusion
These results suggest that blockade of KCa3.1 suppresses plaque instability at the advanced stage of atherosclerosis by promoting polarization of macrophages toward an M2 phenotype.
Abstract 13250: Gender Differences in Asymptomatic Carotid Artery Stenosis; the Association of Age and Smoking With Disease Progression in Males
Authors: Girn Hartaj , Tun Han , Wee David , Clavijo Leonardo , Shavelle David , Garg Parveen
Published: April 2024

Background:
A direct relationship exists between internal carotid artery (ICA) disease progression and stroke incidence. For asymptomatic patients with known ICA disease, there is no proven surveillance strategy. It remains unclear which individuals are at greater risk for disease progression, and whether there are gender-specific risk factors. We examined clinical characteristics associated with ICA disease progression in men and women undergoing carotid duplex ultrasound (CDU) surveillance.

Methods:
We retrospectively studied 289 patients with known ICA stenosis at baseline who underwent CDU from 2008-2014 and had at least one other CDU ≥11 months later. Categories of stenosis included minimal (0-15%), mild (16-49%), moderate (50-79%), and severe (80-99%). Symptomatic patients (stroke or TIA within 6 months), those with severe baseline stenosis, and arteries with prior interventions were excluded. The primary outcome was progression of stenosis to a level of moderate or higher. Baseline clinical data was recorded, and logistic regression analysis was performed.

Results:
Twenty-seven (23%) of 116 females and 30 (17%) of 173 males had progression of ICA stenosis (p=0.21). Females with disease progression were more likely to have moderate baseline stenosis (52% vs 26%, p = 0.01) compared to mild or minimal. Males with disease progression were older (74y vs 70y, p < 0.04), more likely to be current or past smokers (66% vs 44%, p = 0.03), and more likely to have moderate baseline stenosis (50% vs 23 %, p<0.003). Multivariate analysis in males showed age, smoking, and moderate baseline stenosis to be independent predictors of disease progression.

Conclusion:
There was no significant difference in proportion of disease progression between genders. In addition to relying on baseline stenosis for both genders, our findings suggest a role for age and smoking history to help determine effective surveillance protocols for monitoring ICA disease progression in males.
Abstract 13253: Pattern of Cardiac Output vs O2 Uptake Ratio During Maximal Exercise in Heart Failure With Reduced Ejection Fraction: Pathophysiological Insights
Authors: Generati Greta , Bandera Francesco , Pellegrino Marta , Labate Valentina , Carbone Francesco , Alfonzetti Eleonora , Guazzi Marco
Published: April 2024

Background:
the oxygen uptake (VO2) response to exercise, measured during cardiopulmonary exercise testing (CPET), has prognostic value in heart failure (HF). The increase in VO2 is due to the increase in cardiac output (CO) and arterial-mixed venous oxygen content difference (C(a-v)O2). How much (C(a-v)O2) contribute to VO2 increase may be estimated by the CO/VO2 ratio. Aim: To study the cardiac and functional phenotype associated with CO/VO2 ratio at peak exercise in HF with reduced ejection fraction (HFrEF).

Methods:
104 HFrEF patients (mean age 64±11 y, male %, ischemic etiology 68%, mean LVEF 34±9%) underwent a maximal CPET (incremental ramp protocol) combined with exercise-echo.

Results:
Study population was divided into 2 groups according to the peak exercise CO/VO2 (cutoff 0.49, CO/VO2 median value) Group A (n=52) with CO/VO2 <049 and B (n=52) with CO/VO2 ≥0.49. Despite similar peak VO2 (13.8 vs 12.6 mL/min/kg p=ns) patients with impaired CO exercise response (Group A) showed worse cardiac remodeling (LVEDV indexed 101±33 vs 91±23 mL/m2 p=0.09, E/e’28±15 vs 22±11 p=0.02) and more severe mitral regurgitation at rest and peak exercise (ERO rest 22±10 16±9 mm2 p=0.02, peak 33±13 vs 25±12 mm2 p=0.03). Group A patients exhibited also more impaired right ventricular function (TAPSE rest 17±5 vs 19±4 mm p=0.0001, peak 19±5 vs 21±4 p=0.04) associated with ventilatory inefficiency (VE/VCO2 slope 36±11 vs 31±7 p=0.01). The two Groups presented with similar average Hb levels. Conclusions: In advanced HF population, the worse exercise performance is associated witha reduced CO /VO2 ratio during maximal exercise, that for a similar peak VO2 as compared to the population with a high CO/VO2 ratio, is suggestive of "optimal" peripheral O2 extraction as compensation to a reduced O2 delivery.
Abstract 13324: Outcomes of Endovascular Therapy and Intravascular Ultrasound Findings for Thromboangiitis Obliterans (Buerger’s Disease)
Authors: Kawarada Osami , Kume Teruyoshi , Harada Koichiro , Noguchi Teruo , Ogawa Hisao , Yasuda Satoshi
Published: April 2024

Backgrounds:
With the advancement of endovascular therapy for peripheral artery disease, thromboangiitis obliterans (TAO) patients might be able to benefit from endovascular therapy. We sought to investigate contemporary outcomes of endovascular therapy and intravascular ultrasound (IVUS) findings for TAO patients.

Methods:
This study included 21 consecutive limbs in 17 patients (mean age, 47±8 years) undergoing endovascular therapy between April 2007 and February 2015. Subjects’ clinical symptoms included a broad spectrum such as critical ischemia and claudication in the lower and upper limbs.

Results:
The extents of lesions were classified into crural type in 7, femorocrural type in 7, femoropopliteal type in 2, and radiopalmar/ulnopalmar type in 5. A total of 50 arteries and 1 graft were targeted. Successful revascularization was achieved in all limbs. Subacute thrombosis was observed in 4.8% (1 case) that was successfully managed by reintervention. Rutherford category significantly decreased after revascularization (Pre; 4.2±1.1, Post; 0.3±0.6, P<0.001). During a mean follow-up of 18.2±19.9 months (range, 2-96), clinical benefits was sustained although 29% (6 limbs) required a clinically-driven reintervention. IVUS optionally performed in 15 limbs revealed unique findings including “bulls-eye appearance”, “lotus-root appearance” and “grape branch appearance”. Out of a variety of IVUS findings, dissection and undulation yielded a trend toward a higher incidence of reintervention or reocclusion.

Conclusion:
In our series, current endovascular therapy could serve as a potential option for TAO patients with lower and upper limb symptoms. Accumulating IVUS findings might lead to understand pathophysiology of TAO and predict the outcome of endovascular treatment.
Abstract 13341: Homoarginine Supplementation Improves Cardiac Function in a Murine Model of Ischaemic Heart Failure
Authors: Atzler Dorothee , McAndrew Debra J , Crabtree Mark , Hale Ashley , Bailey Jade , Cordts Kathrin , Schneider Jürgen E , Zervou Sevasti , Schwedhelm Edzard , Neubauer Stefan , Lygate Craig A
Published: April 2024

Introduction:
Homoarginine (HA) is an emerging biomarker with low levels associated with increased risk of stroke, myocardial infarction and heart failure (HF) in epidemiological studies. Recently, we identified HA as an independent predictor of mortality in patients with HF. We therefore hypothesized that HA supplementation might be beneficial in a murine model of chronic heart failure.

Methods:
C57BL/6J mice were treated with 14 mg/L HA in drinking water for 4 weeks prior to coronary artery occlusion to induce infarction. Infarct size and HF severity were assessed 6 weeks later by cine-MRI and LV haemodynamics under isoflurane anaesthesia. HA and biopterins were measured using LC-MS/MS and HPLC. Protein S-nitrosylation (SNO) was quantified using biotin switch assay.

Results:
We first established that HA supplementation significantly increased both plasma and myocardial HA levels in normal C57BL/6J mice (mean±SEM 0.29±0.03 vs. 0.89±0.07 μmol/L and 8.8±1.4 vs. 24.4±3.4 nmol/g protein; n=5-10; P<0.01), without affecting mean arterial pressure (76±1 vs. 73±2 mmHg; n=5-6; P=0.23). Infarct sizes were retrospectively matched between control and HA groups (mean 39±2%) and both developed profound LV remodelling (i.e. hypertrophy and dilatation), but to a similar extent. HA-treated mice had improved LV systolic pressure (83.4±1.3 vs. 87.6±1.3 mmHg), contractility (dP/dtmax 4636±238 vs. 5515±270 mmHg/s), relaxation (dP/dtmin -3183±225 vs. -4029±302 mmHg/s) and β-adrenergic responsiveness (+928±184 vs. +1906±327 mmHg/s; n=21-23; all P<0.05). HA-treated hearts showed an increase in tetrahydrobiopterin levels (1.24±0.34 vs. 3.15±0.41 pmol/mg protein; n=4-6, P<0.01) and elevated global SNO (0.98±0.04 vs. 1.76±0.25; n=7/7; P<0.05), but with no change in nitric oxide synthase protein or activity.

Conclusions:
HA supplementation improves LV haemodynamic function and contractile reserve in mice with chronic HF, potentially via altered redox regulation or SNO status. Our data suggest HA is more than a simple biomarker, since higher levels directly influence HF pathophysiology. Further studies aimed at clinical translation are merited.
Abstract 13413: Silent Cerebral Ischemic Lesions After Atrial Fibrillation Ablation Among Oral Anticoagulants: Predictors of Diffusion-Weighted Imaging-Positive Lesions and Follow-up Study
Authors: Nakamura Kohki , Naito Shigeto , Minami Kentaro , Sasaki Takehito , Goto Eri , Yamaguchi Yoshiaki , Shimizu Satoru , Senga Michiharu , Yano Toshiaki , Take Yutaka , Kumagai Koji , Funabashi Nobusada , Kobayashi Yoshio , Oshima Shigeru
Published: April 2024

Purpose:
We aimed to identify the predictors of silent cerebral ischemic lesions (SCILs) detected on diffusion-weighted imaging (DWI) after catheter ablation of atrial fibrillation (AF) in patients with oral anticoagulants (OACs), and to determine whether postablation DWI-positive lesions develop into established cerebral infarcts or not on follow-up magnetic resonance imaging (MRI).

Methods:
This study prospectively included 183 consecutive AF patients (65±9 years; 133 males; paroxysmal/persistent/long-standing persistent AF [LSP-AF], 93/58/32) who received OAC therapy more than 3 weeks before an AF ablation and underwent MRI on the next day after the procedure. Warfarin (n=30; group W) was continued, while dabigatran (n=30; group D), rivaroxaban (n=62; group R), and apixaban (n=61; group A) were discontinued on the day of the procedure. Just after the femoral venous puncture during the procedure, a heparin bolus of 5000 units in group W and 10000 units in the others was given, followed by a continuous and additional bolus infusion of heparin to maintain an activated clotting time of 300-350 seconds. OAC therapy was continued for at least 3 months after the procedure in all patients.

Results:
A total of 38 lesions in 26 asymptomatic patients (14.1%) were detected on DWI. The incidence of SCILs was 10.0% in group W, 30.0% in group D, 8.1% in group R, and 14.8% in group A, respectively. The BNP level and percentage of patients with LSP-AF, dabigatran, and electrical cardioversion during the procedure were significantly higher in the patients with SCILs than in those without (all P<0.05). In a multivariate logistic regression analysis, LSP-AF and the use of dabigatran were significant positive predictors of SCILs (odds ratios, 5.736 and 4.295; 95% confidence intervals, 2.163-15.212 and 1.541-11.966; P<0.001 and 0.005). Of the 26 patients with SCILs, 8 with 11 lesions underwent follow-up MRI 161±54 days after the procedure. All 11 DWI-positive lesions disappeared and none resulted in subsequent infarcts on follow-up MRI.

Conclusions:
LSP-AF and dabigatran use were high risk factors for SCILs after AF ablation among the patients with OACs. However, no SCILs developed into chronic cerebral infarcts under continuous oral anticoagulation following the ablation.
Abstract 13415: Predictive Value of Glomerular Filtration Rate-Adjusted Contrast Volume for Contrast-Induced Acute Kidney Injury After Percutaneous Coronary Intervention
Authors: Nakamura Haruo , Otsuka Kenichiro , Yamaguchi Tomohiro , Ishikawa Hirotoshi , Katayama Hisashi , Takeda Hisateru , Fujimoto Kohei , Yoshiyama Minoru , Kasayuki Noriaki
Published: April 2024

Introduction:
Contrast volume (CV) to estimated glomerular filtration rate (eGFR) ratio has been known as a useful predictor of contrast-induced acute kidney injury (CI-AKI) after percutaneous coronary intervention (PCI). However, a cutoff value of CV/eGFR has not been established.

Hypothesis:
We investigated the clinical predictors and predictive value of CV/eGFR for CI-AKI in patients with coronary artery disease (CAD) underwent PCI.

Methods:
This study consists of 479 hemodynamically stable CAD patients (mean age: 73±10 years) underwent PCI. Patients, and target lesion characteristics were obtained. The primary endpoint was the occurrence of CI-AKI defined as an increase in serum creatinine of 0.5 mg/dl or 25 % within 48 hours after contrast injection. Logistic regression analysis was used to estimate the association of clinical risk factors with development of CI-AKI. Receiver-operating characteristic curve (ROC) analysis was performed to determine the predictive value of CV/eGFR for CI-AKI.

Results:
Mean procedural CV was 93±38 ml. CI-AKI was occurred in 19 patients (3.9%). Multivariate logistic regression analysis showed that higher CV/eGFR (odds ratio; 1.8, 95% confidence interval; 1.03-2.98; p=0.03) was a statistically significant predictor of CI-AKI independent other risk factors (Table). Using ROC analysis for prediction of CI-AKI, the area under the curve was 0.67, and the best cutoff value of CV/eGFR was 1.64 (sensitivity was 8.0%, specificity was 98%, positive and negative predictive values were 58% and 73%, respectively).

Conclusions:
The results of this study suggest that high CV/eGFR is a predictive marker for CI-AKI after PCI independent of other clinical risk factors. Reducing a CV less than 1.64 of eGFR might be valuable in preventing CI-AKI after PCI.
Abstract 13554: Left Atrial Function in Children by Volume and Strain Analysis: Impact of Congenital Aortic Stenosis
Authors: Shakti Divya , Freidman Kevin G , Harrild David M , Gauvreau Kimberly , Geva Tal , Colan Steven D , Brown David W
Published: April 2024

Background:
Left atrial (LA) function by volume and strain analysis in children has been little studied. LA dysfunction related to aortic stenosis has been reported in adults.

Hypotheses:
1. LA volume and strain analysis is feasible and reproducible in normal children.

2. Children with isolated congenital aortic stenosis (AS) as compared to matched controls have higher maximal LA volume (LAV) and lower total longitudinal LA strain.

Methods:
Retrospective chart review and offline analysis of 2D echocardiogram images for phasic LAVs, volume indices, and longitudinal LA strain (Fig 1) by speckle tracking (TomTec software) in: 1. Healthy children with a normal echocardiogram; and, 2. Children ≥1 years of age with significant (≥ moderate) isolated AS. AS cases were compared with age, gender and BSA-matched normal controls.

Results:
There were 67 normal subjects [age: 10.5 (1.3-22.1) yrs; 50 males, 17 females; BSA 1.22 (0.44-2.39) m2] studied. No significant inter-observer and intra-observer differences were noted in normal subjects (Fig 2). Between June 2004 and October 2012, there were 41 eligible AS cases [Age: 11.7 (1.6-26.8) yrs; 32 males, 9 females] with median maximal Doppler aortic stenosis gradient of 63 (43-94) mm Hg. Significantly higher phasic indexed LAVs and indexed active LA stroke volume (pump function) and lower strain values for LA reservoir and conduit function were noted in AS cases (Fig 2).

Conclusions:
LA volume and strain analysis is reproducible and feasible in children. Children with significant AS have abnormal LA function with higher phasic LA volumes, higher LA pump function, and lower strain-derived reservoir and conduit LA function.
Abstract 13566: A Novel New Chemical Entity, Gemcabene, Shows Significant Lipid Regulation in PPAR-α Knock-out Mice, Supporting a Mechanism Independent of PPAR-α
Authors: Bisgaier Charles L , Srivastava Rai Ajit
Published: April 2024

Background:
In vitro and cell-based assays with a lipid lowering agent, gemcabene (Gem), ruled out a direct activation of PPAR-α, although some PPAR-α target genes were modulated in vivo. Therefore, PPAR-α may not be required for the in vivo lipid lowering efficacy of Gem.

Experiment & Results:
WT and PPAR-α KO mice were administered Gem (0.3%), Wy14643 (0.1%), a reference PPAR-α agonist, and a clinical lipid regulator, Gemfibrozil (0.3%) as diet admixtures for 8 days. PPAR-α KO mice exhibited a phenotype consistent with absence of PPAR-α, such as increased plasma triglycerides (TG), VLDL-C, LDL-C, HDL-C, and apoCIII. Hepatic apoCIII mRNA (negatively regulated by PPAR-α) showed upregulation in PPAR-α KO mice compared to WT. In WT mice, there was no change in liver to body weight ratio in the Gem-treated group, but a marked increase (212%) in the Wy14643-treated-group and marginal increase (22%) in gemfibrozil-treated mice. In WT, hepatomegaly was observed only in the Wy14643-treated group, which was associated with peroxisome proliferation, and a 20-fold increase in the PPAR-α target gene, acyl CoA oxidase (ACO). Absence of hepatomegaly in the Wy14643-treated PPAR-α KO mice and no change in ACO mRNA supported PPAR-α mediated effect of Wy14643. In WT, Gem and gemfibrozil showed a 3-fold increase in ACO mRNA. Gem lowered VLDL-C (-47%), LDL-C (-22%), and TG (-46%) in PPAR-α KO mice, suggesting a PPAR-α independent effect on circulating lipids. Wy14643 and Gem significantly reduced apoCIII by -39% and -24% in WT, and -20% and -16% in PPAR-α KO mice, respectively. ApoCIII mRNA was reduced -12% (NS) in Gem-treated and significantly by -46% in Wy14643-treated WT-mice. In KO mice, apoCIII mRNA was reduced by -8% (NS) by Gem and significantly by -20% by Wy14643. ApoCIII mRNA is a direct target of PPAR-α while plasma apoCIII level is influenced by several factors. Wy14643 induced hepatic LPL mRNA in WT, but not in PPAR-α KO mice. Interestingly, hepatic PPARγ expression showed increased level in the PPARα KO mice, suggesting the regulation of the two isoforms may be interdependent.

Conclusions:
Taken together, these studies demonstrate that the lipid lowering efficacy of Gem occurs in a PPAR-α -independent manner in vivo.
Abstract 13611: Adherence to Non-VKA Oral Anticoagulant Medications Based on the Pharmacy Quality Alliance Measure
Authors: McHorney Colleen , Crivera Concetta , Laliberté François , Nelson Winnie W , Germain Guillaume , Bookhart Brahim K , Martin Silas , Schein Jeffrey , Lefebvre Patrick , Deitelzweig Steven
Published: April 2024

Introduction:
CMS Star Ratings help inform beneficiaries about the performance of health and drug plans. Medication adherence and other pharmacy measures are currently weighted at nearly half of a Part D plan’s Star Ratings. Two, 3, 4 and 5 Star Ratings are based on achievement of adherence threshold levels (e.g. 74%, 79%, 82%, and 85% for oral diabetes medications). Including the adherence to non-VKA oral anticoagulant (NOACs) as a measure in the Star Ratings program may increase a plan’s incentives to improve patient adherence.

Objective:
To assess the adherence to medication of patients who used the NOACs rivaroxaban, dabigatran, or apixaban in 2014 based on the Pharmacy Quality Alliance (PQA) adherence measure.

Methods:
Healthcare claims from the Humana database between 07/2013 and 12/2014 were analyzed. Adult patients with ≥2 dispensings of NOAC agents in 2014, at least 180 days apart between two NOAC dispensings in 2014 (a criterion to include chronic users), with >60 days of supply, and ≥180 days of continuous enrollment prior to the index NOAC were identified. PQA measure was calculated as the percentage of patients who had a proportion of days covered (PDC) ≥80%. PQA measure was compared between rivaroxaban and each of the other two groups using chi squared tests. Multivariate logistic regression analyses were also conducted adjusting for baseline confounders.

Results:
A total of 11,095 rivaroxaban, 6,548 dabigatran, and 3,532 apixaban users were identified. Based on the PQA adherence measure (PDC ≥0.8), a significantly higher proportion of rivaroxaban users (72.7%) was found to be adherent compared to dabigatran (67.2%: p<.001) and apixaban (69.5%: p<.001) users. Compared to apixaban users, the adjusted likelihood of being adherent was significantly higher for rivaroxaban users (unadjusted OR: 1.17, p-value<.001; adjusted OR: 1.20, p-value<.001), and significantly lower for dabigatran users (unadjusted OR: 0.90, p-value=0.019; adjusted OR: 0.85, p-value<.001).

Conclusion:
Using the PQA’s adherence measure, rivaroxaban users were found to have a significantly higher adherence compared to apixaban and dabigatran users. Healthcare providers should consider the impact of anticoagulation selection on their ability to achieve quality metrics.
Abstract 13644: The Effect of Computational Fluid Dynamics Modeling Assumptions in Endothelial Shear Stress Calculations derived From Coronary Computed Tomography Angiography
Authors: Giannopoulos Andreas A , Chatzizisis Yiannis S , Maurovich-Horvat Pal , Antoniadis Antonios P , Cai Tianrun , Hoffmann Udo , Steigner Michael L , Rybicki Frank J , Mitsouras Dimitrios
Published: April 2024

Background:
Low endothelial shear stress (ESS) is associated with coronary plaque progression and high-risk plaque features. Coronary ESS profiling requires the three-dimensional luminal geometry and Computational Fluid Dynamic (CFD) assumptions to successfully model coronary blood flow.

Hypothesis:
To examine whether two typical CFD modeling assumptions, namely the exclusion of side branches and the blood model used, alter the determination of those arterial regions that are exposed to low ESS.

Methods:
Five excised human hearts were imaged with 64-detector row CT. Coronary arteries >1 mm in diameter were segmented and the coronary tree lumen was reconstructed with and without side branches. ESS was calculated for 3 models: a) the entire tree and a non-Newtonian blood model (reference standard) b) the entire tree and a Newtonian blood model and c) major coronaries only (no side branches) and a non-Newtonian blood model (Fig panel A). ESS was compared in each major coronary artery amongst models using Pearson’s correlation and via sensitivity and specificity to detect those 3 mm sections in the coronary circulation that contained the 10% of endoluminal surface with lowest ESS values. For sensitivity and specificity the first model (a) was considered the reference standard.

Results:
The Newtonian assumption for blood induced minimal change in ESS pattern other than a relative scaling of values. The exclusion of side branches however induced large, coronary-segment specific non-linear changes in both pattern and value. With no side branches, sensitivity and specificity to identify low ESS regions were 78% and 88%. With Newtonian blood and side branches, sensitivity and specificity were 89% and 98% (Fig panel B).

Conclusion:
Side branches are important for identifying areas of low ESS while the assumption that blood model behaves as a Newtonian fluid has negligible effect.
Abstract 13690: Longitudinal and Segmental Right Ventricular Free-Wall Strain Before and After Pulmonary Thromboendarterectomy in Patients With Chronic Thromboembolic Pulmonary Hypertension
Authors: Wong Darrin , Yousefian Omid , Auger William , Dittrich Teri , Madani Michael , Daniels Lori , Raisinghani Ajit , DeMaria Anthony , Blanchard Daniel
Published: April 2024

Introduction:
Echocardiographic assessment of right ventricular (RV) function is problematic. We sought to evaluate RV systolic function in chronic thromboembolic pulmonary hypertension (CTEPH) using 2D speckle tracking and strain analysis. We assessed longitudinal & segmental RV free-wall strain before and after pulmonary thromboendarterectomy (PTE) in patients with CTEPH.

Hypothesis:
We hypothesized systolic strain would improve after PTE.

Methods:
Peak systolic strain (%) of the RV free-wall and its segments (basal, mid, apical) was measured by 2D echocardiography in 127 consecutive CTEPH patients (52 ± 14 years, 49% female) with adequate images pre- & post- PTE. Strain was measured 9.7 ± 17.3 days pre- and 11.3 ± 17.0 days post-PTE using Epsilon Imaging EchoInsight software.

Results:
Mean longitudinal strain of the RV remained the same pre-PTE compared to post-PTE (-11.4 ± 5.7 to 11.2 ± 5.6%, p = 0.67), but basal & mid RV free-wall strain worsened (less negative): -17.1% to -14.1% (p=0.003) and -12.8% to -10% (p=0.001) respectively after PTE. Apical RV free-wall strain improved (more negative): -3.7% to -9.2% (p<0.001) (Table 1). Pre-PTE, mean RV free-wall strain correlated significantly with pulmonary vascular resistance (PVR) (Table 2) and mean pulmonary artery pressure (mPAP), but this relationship disappeared after PTE.

Conclusions:
RV free wall basal and mid segment systolic strain worsened (less negative) soon after PTE, while the apical segment strain improved (more negative). The reasons for these differences are unclear, but may vary due to RV stunning and changes in LV filling. RV mean free-wall strain correlates significantly with PVR pre- but not post-PTE.
Abstract 13860: The Mitochondria-targeted Antioxidant Therapy Improves Age-related Cardiovascular Dysfunction
Authors: Owada Takashi , Saitoh Shu-ichi , Yamauchi Hiroyuki , Miura Shunsuke , Machii Hirofumi , Takeishi Yasuchika
Published: April 2024

Senescence is a major factor to increase oxidant stress in mitochondria, which contributes to the pathogenesis of heart diseases. We postulated that scavenging effect of superoxide targeted in mitochondria would have benefit in the aged heart. Increased levels of superoxide and NADPH oxidase activity were appeared in cardiac myocytes isolated from old mice (70 W) compared to those in young mice (8 W) (superoxide: 2.6±0.4 vs. 1.2±0.2 nmol/mg protein; NADPH oxidase activity: 2654±282 vs. 1124±156 RLU, p<0.01, n=16, respectively). In old mice treated with mitochondria-targeted antioxidant, MitoTEMPO, co-infusion using minipump (180 μg/kg/day, 28 days), levels of superoxide and NADPH oxidase activity decreased (0.2±0.2 nmol/mg protein and 342±45 RLU, p<0.01, respectively). Treatment with MitoTEMPO improved left ventricular ejection fraction from 48±5% to 62±5% (p<0.01) with old mice in echocardiography. Endothelium-dependent coronary artery vasodilation, eNOS and Sirt1 levels were lower in old mice compared to those in young mice, which were improved by MitoTEMPO treatment (n=12 each, Figures). %SOD activity in cardiac mitochondria was lower in old mice compared to that in young mice (38.7±3.7 vs. 65.0±5.2%, p<0.05), which were improved by MitoTEMPO treatment (61.2±4.1%). Treatment with MitoTEMPO in old mice improved decreased oxygen consumption rate in complex I and III of cardiac mitochondria to the level of those in young mice. Resolution of mitochondrial oxidant stress by MitoTEMPO in old mice restored cardiovascular function to the same magnitude observed in young mice. Therefore, antioxidant strategy targeting mitochondria could have therapeutic benefit in heart diseases with senescence.
Abstract 13870: Routine Follow Up Coronary Angiography versus Clinical Follow Up Only in Patients With Multi-vessel Disease Following Percutaneous Coronary Intervention With Drug-eluting Stents: 3-year Clinical Follow Up Results
Authors: Rha Seung Woon , Choi Byoung Geol , Choi Se Yeon , Byun Jae Kyeong , Na Jin Oh , Choi Cheol Ung , Lim Hong Euy , Kim Jin Won , Kim Eung Ju , Park Chang Gyu , Seo Hong Seog , Oh Dong Joo
Published: April 2024

Background:
It is unclear whether the routine follow up (FU) coronary angiography (CAG) regardless of patient’s symptoms after successful percutaneous coronary intervention (PCI) with drug-eluting stents (DESs) in patients (pts) with multi-vessel disease (MVD) is beneficial or not.

Methods:
The study population consisted of 642 consecutive MVD pts underwent PCI with unrestricted utilization of DESs from January 2004 to May 2011. Routine FU CAG was performed between 6 to 9 months following index PCI and was decided by individual physician’s discretion. Rests of the pts were clinically followed and ischemic driven events were captured. Clinical events including mortality, myocardial infarction and clinically driven PCI before 9 months were excluded in both groups. Cumulative clinical outcomes up to 3 years were compared between the Routine CAG group (n=374 pts) and the Clinical FU group (n= 268 pts). To adjust potential confounders, a propensity score matched (PSM) analysis was performed using the logistic regression model.

Results:
After PSM analysis, 2 propensity-matched groups (193 pairs, n = 386 pts, C-statistic=0.744) were generated and the baseline characteristics of the two groups were balanced. At 3 years, the incidence of target lesion revascularization (TLR) and target vessel revascularization (TVR) and major adverse cardiac events (MACEs) was higher in the Routine CAG group than the control group (Table).

Conclusions:
Despite the expected beneficial effects, routine FU CAG following index PCI with DESs in MVD pts was associated with higher incidence of repeat PCI including TLR and TVR and MACE up to 3 years.
Abstract 13911: ELABELA/Toddler (Apela), is an Endogenous Ligand of the Human Apelin Receptor and is Reduced in Pulmonary Arterial Hypertension
Authors: Yang Peiran , Maguire Janet J , Kuc Rhoda E , Southwood Mark , Morrell Nicholas W , Davenport Anthony
Published: April 2024

Introduction:
The apelin receptor is proposed as a therapeutic target in pulmonary arterial hypertension (PAH). The apelin peptide knockout mouse does not recapitulate the apelin receptor knockout mouse however this may be explained by the recent identification of a novel peptide, ELABELA/toddler/apela (ELA), identified in a previously designated non-coding region. We have previously demonstrated ELA expression localised to endothelial cells in human cardiovascular tissues and ELA binding to the human expressed apelin receptor. It remains to be determined whether the pharmacology of ELA is comparable to apelin and whether ELA is detectable in human plasma and, more importantly, whether ELA expression is altered in PAH where apelin expression is reduced.

Hypotheses:
We hypothesised that ELA binds to the apelin receptor in human heart, activates both G protein-dependent and -independent signalling, is present in human plasma and is reduced in PAH.

Methods:
Competition binding assays were performed in human heart. The potency (pD
2
) of ELA-32 and [Pyr
1
]apelin-13 was determined in cAMP, β-arrestin and internalisation assays in cells expressing the human apelin receptor. Levels of ELA and apelin were measured in human plasma samples. The presence and absence of ELA immunostaining was scored in pulmonary vessels (≤100μm diameter) in sections of human lung from PAH patients and controls (IRB approval) and compared using Fisher’s Exact Test.

Results:
ELA-32 competed for binding of [
125
I][Pyr
1
]apelin-13 with an affinity of 0.21±0.06nM (n=3). Both ELA-32 and [Pyr
1
]apelin inhibited cAMP production (pD
2
=9.36±0.11, n=6; 9.61±0.12, n=5), elicited β-arrestin recruitment (9.13±0.18, n=16; 8.28±0.05, n=21) and receptor internalization (9.16±0.10, n=8; 8.55±0.07, n=7). ELA peptide was detectable in human plasma (0.49±0.05nM, n=25). The proportion of ELA-negative lung vessels was significantly increased in PAH (n=10) compared to controls (n=4) (p<0.01).

Conclusions:
This study further characterizes ELA receptor pharmacology, signalling and plasma levels. We report for the first time down-regulation of ELA peptide in human disease. These findings support the apelin receptor as a target in the treatment of PAH.
Abstract 13938: Relationships Between ‘Mediterranean’ and ‘Western’ Dietary Patterns and Biomarkers Associated With Increased Cardiovascular Risk in Patients With Stable Coronary Heart Disease in the Global STABILITY Trial
Authors: Stewart Ralph A , White Harvey D , Benatar Jocelyne , Danchin Nicolas , Hagström Emil , Held Claes , Husted Steen , Lonn Eva , Hadziosmanovic Nermin , Vedin Ola , Watson David , Siegbahn Agneta , Wallentin Lars
Published: April 2024

Introduction:
In the STabilization of Atherosclerotic plaque By Initiation of darapLadIb TherapY (STABILITY) trial greater adherence to a Mediterranean dietary pattern (MD) was associated with major cardiovascular (CV) events (MACE) but there was no association between a ‘Western Diet Score’ (WDS) and MACE. The lowest mortality and MACE was in patients with a MD score (MDS) ≥15.

Hypothesis:
Low adherence to a MD may be associated with higher plasma levels of biomarkers known to predict adverse CV events.

Methods:
At baseline, 15,482 (97.8%) trial participants completed a lifestyle questionnaire. MDS was calculated for increasing consumption of whole grains, fruits, vegetables, legumes, fish, and alcohol, and for less meat. WDS was calculated for increasing consumption of refined grains, sweets and desserts, sugared drinks, and deep-fried foods. In 15,287 of these participants hs C-reactive protein (hs-CRP), hs troponin T (hs-TnT), N-terminal B type natriuretic peptide (NT-proBNP), interleukin-6 (IL-6), cystatin-C, growth differentiation factor-15 (GDF-15) and lipoprotein-associated phospho-lipase A
2
(Lp-PLA
2
) were measured from stored plasma samples taken at baseline. The ratios of the geometric mean level of each biomarker by diet group are reported adjusted for age, gender, darapladib treatment, geographic region, markers of disease severity, and CV risk factors including body mass index, diabetes, hypertension, and low and high-density lipoprotein cholesterol.

Results:
Lower MDS (13-14/ ≥15 and ≤12/ ≥15 respectively) was associated with higher hs-CRP 1.12 (95%CI 1.05; 1.19), 1.18 (1.11; 1.25), cystatin-C 1.01 (1.00; 1.02), 1.03 (1.01; 1.04), GDF-15 1.05 (1.02; 1.07), 1.06 (1.04; 1.09) and LpPLA2 1.02 (1.01; 1.04), 1.04 (1.02; 1.06) after adjusting for all co-variables (p<0.01 for all). IL-6, hs-TnT and NT-proBNP were not independently associated with MDS. WDS was not independently associated with higher plasma levels of any biomarkers.

Conclusions:
MD may be associated with lower CV risk in part by effects on inflammatory activity and pathways of cellular function independent of plasma lipids. Greater consumption of food in the WDS was not associated with adverse CV events or with biomarkers known to be associated with risk.
Abstract 13964: Effect of Coronary Sinus Ring Implantation on Reduction of Pulmonary Artery Systolic Pressure
Authors: EL-Shurafa Haytham S , AL-Hebaishi Yahya , AL-Masood Ali , AL-Moghairi Abdulrahman , AL-Amri Hussin , AL-Khushail Abdullah , AL-Fagih Ahmed
Published: April 2024

Objectives:
The purpose of paper is to report the mid-term(mean of 24 months) outcome of MV annuloplasty using Carillon coronary sinus (CS) Device therapy in reducing the pulmonary artery systolic pressure(PASP) at PSCC, Saudi Arabia.

Background:
Carillon CS Device is one of the devices used for treatment of severe functional symptomatic mitral regurgitation in heart failure patients, which is associated with high mortality and difficulty in controlling heart failure symptoms. This study provides a snapshot of the real-world clinical demographic data and outcome on reducing the PASP in a single center using this treatment modality.

Methods:
A total of 30 patients with severe symptomatic mitral valve regurgitation (MR) underwent Carillon CS Device therapy at Prince Sultan Cardiac Center.

All patients were in New York Heart Association functional class III or IV, and 82% of patients had an ejection fraction ≤25%.

Results:
The Carillon CS Device implant rate was 80%. A total of 1 patient (3%) died within 30 days after the procedure. The mean Intensive care unit and hospital length of stay was 3 days. None of the patients required mitral valve surgery after the MV ring device implant procedure. There was significant drop in the PASP , compared to base line seen (from 60.4±11.9 to 43.0±13.3 (p<0.009)) . 85% of patients had New York Heart Association functional class II or class I, at a mean follow up of 18 months .Six-minutes-walk-test improved 193± 7 m, to 470±5 m (p<0.002).

Conclusions:
Carillon CS Device therapy used in high risk severe functional symptomatic MR is promising with a low rate of hospital mortality and significant improvement of symptoms and PASP .