bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18610: Left Atrial Thrombus Formation After the Left Atrial Appendage Exclusion With a Novel Endoepicardial Suture Device (LARIAT®)
Authors: Vallakati Ajay , Reddy Madhu Y , Gibson Doug , Price Matthew , Feldman Ted , Knight Bradley , Cheng Jie , Lee Randall , Earnest Matthew , Nath Jayant , Ferrell Ryan , Atkins Donita , Bommana Sudharani , Loyolka Pranav , Lakkireddy Dhanunjaya
Published: April 2024

Introduction:
There is no data reported on the occurrence of left atrial (LA) thrombus after LA appendage (LAA) closure with Lariat suture ligation device. We intend to identify the incidence and describe the clinical course of LA thrombi after Lariat procedure.

Methods:
We performed a multicenter observational study including all patients who underwent Lariat LAA exclusion. Patients underwent routine post-procedural TEE at approximately 1, 3 and 12 months follow-up. Additional TEEs were obtained as deemed necessary clinically. All patients in whom a LA thrombus was detected on TEE images were included in the study. Demographic characteristics, procedural variables, time of detection of LA thrombus were noted. Clinical course including duration of anticoagulation, serial TEEs and complications during follow up were recorded and analyzed.

Results:
Of the 1056 patients who underwent Lariat procedure, 8 patients (6 males; 2 females) were found to have a LA thrombus (0.007%). Median age, median CHADS2 score, median CHADS-Vasc score and median HASBLED score were 76 years, 3.5, 4.5 and 3 respectively. LA thrombus was detected after median interval of 36 days (IQR 32.5 -262.5). Thrombus was seen in close proximity of the LAA remnant in all patients. It was identified on the first follow-up TEE in all but one. In 1 patient 1.5 cm LA thrombus was seen at 427 days with prior TEEs being clear. Mean diameter of LA thrombus was 1.14 cm ± 0.3. Dabigatran was initiated in 2 patients and warfarin in the rest. After a median duration of 190 days (IQR 86-367.5), resolution of LA thrombus was observed in 7/8 patients. In 1 patient (on warfarin), there was a significant reduction in the size of the thrombus in the first and only TEE obtained 60 days after detection. In 1 patient on dabigatran, delayed resolution of thrombus was seen (occurring at 228days after detection). No embolic events were seen in any of the patients.

Conclusion:
Incidence of LA thrombus is rare after LARIAT LAA exclusion and can be safely managed with oral anticoagulation without any active intervention.
Abstract 18616: NoxA1-Dependent NADPH Oxidase Regulates VSMC Phenotype, Hypertension, and Atherosclerosis
Authors: Sumida Arihiro , Vendrov Aleksandr E , Yuan Jinling , Sun Qi-An , Madamanchi Nageswara R , Runge Marschall S
Published: April 2024

Increased oxidative stress and inflammation are key components in the pathogenesis of atherosclerosis and hypertension. We previously reported that Nox activator 1 (NoxA1) is the functional homolog of p67phox in Nox1 NADPH oxidase activation in mouse vascular smooth muscle cells (VSMCs), and its mRNA and protein expression are induced by TNF-α, a proinflammatory cytokine. Here we investigated the physiological function of NoxA1-dependent NADPH oxidase activity in mouse VSMCs, and NoxA1 expression in human aortic SMCs (HASMCs), in response to TNF-α. Furthermore, we evaluated the role of this enzyme in angiotensin II-mediated hypertension and in atherogenesis in ApoE
-/-
mice.

TNF-α-induced ROS generation was significantly attenuated in NoxA1
-/-
VSMCs compared with the wild-type (p <0.05). NoxA1 deletion also significantly decreased TNF-α-induced DNA synthesis and migration in mouse VSMCs (p <0.05 in each case). In HASMCs, NoxA1 mRNA expression was 10-fold higher than that of p67phox, and NoxA1 mRNA and protein expression were markedly induced by TNF-α (p>0.05 in each case). Angiotensin II infusion for 2 weeks significantly increased systolic blood pressure in wild-type mice, but this response was attenuated in NoxA1
-/-
mice. Atherosclerotic lesion size was reduced by 50% in ApoE
-/-
/NoxA1
-/-
compared with ApoE
-/-
in mice that were fed Western diet for three months. ROS levels in the aortic wall of ApoE
-/-
/NoxA1
-/-
were significantly lower compared with ApoE
-/-
mice. In addition, ApoE
-/-
/NoxA1
-/-
mice had less accumulation of inflammatory CD11b
+
macrophages, CD3
+
T-lymphocytes, and c-kit
+
mast cells in atherosclerotic lesions.

In conclusion, NoxA1-dependent NADPH oxidase regulates oxidative stress, inflammation, angiotensin II-induced hypertension, and atherogenesis in hypercholesterolemic mice, suggesting that selective targeting of NoxA1 is beneficial.
Abstract 18701: Sildenafil Attenuates Ethanol-Induced Myocardial Dysfunction and Cytotoxicity
Authors: Sturz Gregory R , Das Anindita , Hoke Nicholas N , Salloum Fadi N , Kukreja Rakesh C
Published: April 2024

Background:
Ethanol (EtOH) induces cardiotoxicity by increasing apoptosis, free radical formation and lipid peroxidation. Since sildenafil has potent cardioprotective effects through activation of protein kinase G, we hypothesized that treatment with sildenafil would attenuate cardiotoxicity associated with acute EtOH exposure by reducing apoptosis and preserving function.

Methods and Results:
Mice were treated with EtOH (3 g/kg/day, ip) ± sildenafil (0.7 mg/kg, ip) for 3 days. Cardiac function was measured in Langendorff mode. EtOH treatment decreased rate-force product (g·bpm) (270 ± 26, P < 0.01) as compared to control (433 ± 23), which was preserved with sildenafil co-treatment (392 ± 38). EtOH increased myocardial apoptosis (1.42 ± 0.16%; P < 0.001 vs. control 0.05 ± 0.03%), which was attenuated with sildenafil (0.05± 0.05%). Sildenafil increased myocardial PKG activity with (2.6 fold) or without EtOH (4.6 fold). To further understand the mechanism of protection of sildenafil against EtOH cardiotoxicity, primary rat cardiomyocytes were treated with 100 mM EtOH ± 10 μM sildenafil. At 18 h, necrosis (trypan blue staining); mitochondrial membrane potential (mΔΨ, JC-1; aggregates/monomer); and ROS (DCF; F488 AU) were measured.

At 48 h, apoptosis was assessed by TUNEL. EtOH increased necrosis and apoptosis, which were attenuated with sildenafil (Fig 1). EtOH disrupted mΔΨ (EtOH 1.24 ± 0.17, P < 0.001) and increased ROS production (EtOH 156.73 ± 36.91, P < 0.01) compared to control (13.08 ± 1.78 and 28.09 ± 5.75, respectively). Sildenafil preserved mΔΨ (19.29 ± 3.01) and attenuated ROS production (12.38 ± 5.70). Knockdown of PKG with adenoviral shRNA blocked the protective effect of sildenafil whereas overexpression of PKG1α conferred similar protection against EtOH cytotoxicity (Fig 1).

Conclusion:
Sildenafil attenuates the EtOH cardiotoxicity through PKG-dependent maintenance of mitochondrial integrity while preserving cardiac function.
Abstract 18705: Simian Immunodeficiency Virus Induces Pulmonary Arterial Hypertension in Rhesus Macaques: A Hemodynamic Study
Authors: Hu Jian , Tarantelli Rebecca , Simon Marc , Bachman Timothy , Norris Karen , Champion Hunter
Published: April 2024

Background:
Our prior studies have shown that the Cyno Macaques and Resus Macaques infected with simian immunodeficiency virus (SIV) develop pulmonary arterial hyperplasia by histopathology. The hemodynamic changes with infection, however, remain unknown. The purpose of this study was to determine the relationship of the SIV infection and cardiac hemodynamic changes as assessed by invasive right heart catheterization.

Methods:
Five Rhesus macaques underwent pulmonary artery catheterization at baseline and 6 months after infection with SIV. Right atrial pressure (RAP), right ventricular end systolic pressure (RVESP), end diastolic pressure (RVEDP), and mean pulmonary artery pressure (mPAP) were measured directly using a pediatric pulmonary artery catheter. RV dp/dt min, dp/dt max, Tau and contractility index were calculated by Matlab software. In addition, mPAP was calculated in a larger cohort (n=24) by the regression formula: mPAP=RVSP*0.65+0.55 in order to validate this calculation in non-human primates.

Results:
After 6 months of SIV infection, RAP, RVSP, and mPAP increased significantly compared to baseline values. RVEDP trended toward being higher but was not statistically significant from baseline. The RV dp/dt min, dp/dt max and Tau didn’t show significant changes. The contractility index had a markedly decrease with SIV infection compared with baseline. Moreover, direct measure mPAP correlated well with the calculation of mPAP (R
2
=0.954; P<0.0001).

Conclusion:
Based on the presented data we conclude that SIV induces pulmonary arterial hypertension in Rhesus monkeys concordant with the histopathological observation in our prior studies. SIV infection also decreases the RV contractility as well. These data suggest that this may be a viable large animal, preclinical model of PAH with hemodynamics and histology consistent with the human condition.
Abstract 18710: Improvements in Glycemic Control in Type 2 Diabetes Do Not Lead to Reductions in Circulating Cardiac Troponin
Authors: Everett Brendan M , Cook Nancy R , Ridker Paul M , Pradhan Aruna D
Published: April 2024

Objective:
Concentrations of cardiac troponin T, when measured with a high-sensitivity assay (hsTnT), have emerged as a strong marker of cardiovascular mortality, and are frequently elevated in patients with type 2 diabetes. Whether glycemic control affects concentrations of this marker is unknown.

Methods and Results:
We measured hsTnT in patients from the LANCET trial, a 14 week, 2x2 factorial, randomized, placebo-controlled trial of insulin glargine and metformin in early type 2 diabetes. Baseline and 14-week follow up samples were available from 438 participants. At baseline, 408 out of 438 (93.2%) had detectable circulating hsTnT, while 59 (13.5%) had hsTnT levels above the established upper reference limit (≥ 14 ng/L). At baseline, the median (IQR) HbA1c was 6.9% (6.3-7.7%) with no significant differences by treatment group. Statistically significant associations with baseline natural logarithm transformed hsTnT were noted for age (ρ=0.09, P<0.05), but not fasting glucose, HbA1c, body mass index, interleukin-6, or high-sensitivity C-reactive protein (each P>0.26). After 14 weeks of randomly allocated therapy, we observed a significant reduction in HbA1c in all treatment groups except placebo (Figure). In models adjusted for baseline hsTnT and baseline antihyperglycemic therapy we observed no over all change in hsTnT by random treatment allocation (P=0.92) and no individual treatment group differences relative to placebo (Figure; each P≥0.37).

Conclusions:
These data suggest that aggressive glucose control with insulin glargine, metformin, or the combination does not alter concentrations of circulating cardiac troponin T. Our findings are concordant with the results of large randomized controlled trials showing that glycemic control alone may not suffice to substantively lower cardiovascular risk. (Clinicaltrials.gov Identifier:
NCT00366301
)
Abstract 18714: Arterial Stiffness and Subclinical Inflammation in the General Population: The Asklepios Study
Authors: Chirinos Julio , Gillebert Thierry , De Buyzere Marc , Chirinos Diana , Segers Patrick , De Bacquer Dirk , Rietzschel Ernst ,   Asklepios Investigators
Published: April 2024

Background:
Chronic subclinical inflammation is a potentially treatable process that may contribute to arterial stiffening. However, previous studies assessing this relationship have used single inflammatory markers and have not assessed potential gender differences in this relationship.

Methods:
We assessed the relationship between arterial stiffness and inflammation among 2,430 middle-aged adults (51.8% female) enrolled in the population-based Asklepios study in Belgium. Using confirmatory factor analysis, we built a measurement model for inflammation, a latent factor contributing to shared variability in multiple acute-phase reactants (C-reactive protein, interleukin-6, white blood cell count and fibrinogen). We used structural equation modeling to characterize the relationship between inflammation and carotid-femoral pulse wave velocity (CF-PWV), a measure of large artery stiffness.

Results:
Our measurement model demonstrated adequate fit (Comparative fit index=0.996; root mean square error of approximation=0.029; standardized root mean square residual=0.012). In unadjusted models, inflammation was significantly related to arterial stiffness in both men (β=0.26;
P
<0.0001) and women (β=0.21;
P
<0.0001). After adjustment for age, current smoking, body mass index, mean arterial pressure, diabetes mellitus, triglycerides, LDL- and HDL-cholesterol, inflammation was independently related to arterial stiffness in men (β=0.13;
P
=0.007) but not in women (β=0.017;
P
=0.7585). This was true for both pre- and post-menopausal women and regardless of oral contraceptive use.

Conclusions:
Important gender differences exist in the association between inflammation and large artery stiffness. Inflammation is independently associated with large artery stiffness in middle age in men, but not in women.
Abstract 18715: Pituitary Apoplexy Following a Nuclear Stress Test
Authors: Shetty Suchith , D’souza Seema , Moll David , Song Liquin , Kumaradhas Nithya , Gnanaraj Joseph
Published: April 2024

Background:
Regadenoson is an A2A adenosine receptor agonist with weak affinity for A1, A2B and A3 adenosine receptors. Regadenoson(RAD) is used in MPI in patients who are unable to undergo exercise stress test. It acts primarily by activating A2A receptors causing coronary vasodilatation and increase blood flow. RAD has gained popularity since its approval in 2008 for its longer half life, ease of administration and obviating the need to stop beta blockers prior to testing. The common side-effects are dyspnea, headache and flushing. Here we describe the first documented case of pituitary apoplexy following regadenoson stress test.

Case:
Our patient is a 49 year-old female who underwent RAD stress test for evaluation of CAD. Within hours of testing she developed excruciating pressure like headache in peri-orbital and frontal regions. BP was moderately elevated and physical examination, including fundoscopy was normal. CT head showed a 1.3 x 1.4 cm pituitary mass. MRI with gadolinium confirmed a sellar and suprasellar 22 x 16 x 18 mm mass with small element of acute hemorrhage and necrosis suggesting pituitary apoplexy.

Patient subsequently underwent resection of pituitary mass. Pathology revealed pituitary early infarction and hemorrhage.

Conclusion:
RAD induced coronary and possible peripheral vasodilatation is mediated primarily by the A2A adenosine receptor (A2A-AdoR) present in the vascular wall. The A2A-AdoR is widely distributed including the cerebral circulation. The effects of RAD such as arterial vasodilatation, sympathomimetic excitation, inhibition of platelet aggregation, reduced airway hyper-responsiveness, are known to mediate through this receptor. The vasodilatory effect on the cerebral arteries is postulated as the mechanism of headaches in patients receiving RAD. Based on our case findings and mechanism of action of RAD we hypothesize that reduced blood flow in the pituitary gland from vasodilatation and rapid fluctuations in blood pressure from RAD might have precipitated pituitary apoplexy in our patient. This case illustrates that although rare, pituitary apoplexy should be included in the differential diagnosis of patients with persistent headache of more than 30 minute duration after completion of ragedenoson stress test.
Abstract 18798: Gata4 and Gata6 Are Necessary for Neonatal but Not Adult Cardiac Function Under Normal Physiological Conditions
Authors: Prendiville Terence W , He Aibin , Zhou Pingzhu , Von Gise Alexander , Ma Qing , Pu William T
Published: April 2024

Objective:
Fetal inactivation of the cardiac transcription factors Gata4 and Gata6 has been shown to cause postnatal heart dysfunction. However, the postnatal requirement for these transcription factors has not been defined.

Methods:
Using systemic delivery of recombinant adeno-associated virus 9 expressing Cre from the cardiac specific TNNT2 promoter (1.2E x 12VG/gram body weight; n=6), we inactivated floxed Gata4 and Gata6 alleles in neonatal or adult hearts. Left ventricular performance was followed serially using M-mode echocardiography and two-dimensional speckle tracking-derived myocardial tissue deformation (Visualsonics Vevo 2100) under light isofluorane anesthesia. The intervention group was compared to a control AAV-TNNT2 encoding luciferase.

Findings:
In the neonatal heart (P1-P5), effective knock-down of Gata4 and Gata6 (n=6 mice) was confirmed by Western blot and quantitative reverse-transcription PCR of myocardial tissue: We observed a 4.9-fold reduction in Gata4 expression; (95% C.I. +/-1.2) and a 6-fold reduction in Gata6 expression (95% C.I. +/- 1.2). Over the course of 5 days, left ventricular ejection fraction decreased significantly from a mean of 81% to 39% +/- 3% SEM (p<0.0001). Strain analysis confirmed a global reduction in myocardial performance after knock-down. The expression of heart failure markers, m-ANF and MYH7, were markedly up-regulated at 17-fold and 24-fold, respectively.

In the adult heart (postnatal weeks 6-9, n=6), despite a technically successful systemic delivery of rAAV9, no noted left ventricular dysfunction was apparent on subsequent serial follow-up by m-mode echocardiography. Similarly, myocardial performance, as measured by strain & strain rate analysis in the longitudinal, circumferential and radial planes, remained equal in the intervention group to that of the control group.

Conclusions:
AAV9-TNNT2-Cre is an effective means of achieving temporally controlled inactivation of floxed alleles in the postnatal heart. Gata4 and Gata6 are required to maintain normal left ventricular systolic function during neonatal life, but are no longer required in adulthood under normal physiological conditions.
Abstract 18816: Predicting an Accurate Intensity Threshold on LGE-MRI for Identification of Left Atrial Fibrosis
Authors: Khurram Irfan M , Zipunnikov Vadim , Dewire Jane , Beinart Roy , Spragg David D , Marine Joseph E , Berger Ronald D , Halperin Henry R , Calkins Hugh , Zimmerman Stefan L , Nazarian Saman
Published: April 2024

Background:
Late gadolinium enhanced (LGE) MRI identifies left atrial (LA) fibrosis in atrial fibrillation (AF). However, routine measurement of image intensity in “arbitrary units” limits inter-patient and longitudinal comparisons. This study is designed to identify the scar threshold identification on LGE-MRI to improve the uniformity and validity of results.

Methods:
High-resolution navigator-gated LGE-MRI (1.5 Tesla) was performed in 75 patients (31% female, age 62 ± 8 years) prior to the first (60%), second (24%), or third (16%) ablation for AF. Epicardial and endocardial contours were manually drawn around LA myocardium. The image intensity ratio (IIR) was defined as LA myocardial signal intensity for each of 20 sectors on contiguous axial planes divided by the mean LA blood pool image intensity. Intra-cardiac point-by-point sampled electro-anatomical map (EAM) points were registered and superimposed upon the image. Log transformed bipolar voltage was plotted against IIR and the threshold values corresponding to 0.5mV and 0.1mV were identified.

Results:
A total of 8153 EAM points and corresponding image sectors were analyzed. In a generalized estimating equations model accounting for within patient clustering, and adjusting for age, LA volume, mass, BMI, gender, CHADSVasc score, AF type, prior ablation, and the delay time between contrast and image acquisition, each unit increase in local IIR was associated with 91.3% decrease in bipolar LA voltage (P<0.001). The IIR was strongly associated with bipolar voltage on EAM in patients with minimal and extensive LA fibrosis (figure top). IIR thresholds of 0.97 and 1.62 corresponding to 0.5 mV (fig-bottom left) and 0.1 mV (fig- bottom right), respectively, were obtained and showed convergence of the 95% CI and a stable threshold with increasing patients.

Conclusion:
Normalization of LGE-MRI intensity by the mean blood pool intensity results in a stable threshold to identify diffuse fibrosis or dense scar.
Abstract 18820: Bayesian Meta-Analysis of the Novel Oral Anticoagulants versus Warfarin in Patients With Renal Failure
Authors: Lang Christopher , Shim Hye Gi , Arora Rohit
Published: April 2024

The novel oral anticoagulants (NOACS) dabigatran, rivaroxaban and apixaban for prevention of stroke and systemic embolization in atrial fibrillation are attractive alternatives to warfarin. Controversy exists regarding the use of these medication in renal failure. To compare differential benefit, we performed a Bayesian meta-analysis examining the efficacy and safety of the NOACS versus warfarin in patients with renal failure

Methods:
Using data from the 3 major trials investigating the novel oral anticoagulants, we conducted a Bayesian meta-analysis of patients stratified by creatinine clearance of 80 ml/min. The primary endpoints of stroke and systemic embolization were assessed, along with safety endpoints of major bleeding, if available. A Bayesian analysis was performed on each group, defining probabilities of benefit for the posterior probability. From this data, sequential Bayesian meta-analysis was performed and posterior probabilities were obtained.

Results:
Posterior probabilities for stroke and systemic embolization indicate that NOACS in patients with CrCl >80 ml/min have an 74.8% probability of benefit over warfarin. In patients with CrCl 50-80 ml/min there is 95.5% probability of benefit. Patients with CrCl <50 ml/min there is a 93.7% probability of benefit of NOACS over warfarin. Analysis of bleeding events using available data showed a trend towards benefit of NOACS versus warfarin in incidence of major bleeding events.

Conclusions:
The use of novel oral anticoagulants in patients with renal failure confers a high probability of benefit over warfarin in prevention of stroke and systemic embolization. The NOACS appear to have potentially improved bleeding outcomes in this subgroup, though data is limited. This analysis suggests that the novel oral anticoagulants are more effective and are at least as safe in patients with renal failure when compared with warfarin.
Abstract 18828: Comprehensive Lipidomic Analysis of Myocardial and Circulating Acylcarnitine Levels in Patients With Advanced Heart Failure Before and After Mechanical Unloading and Controls
Authors: Moore D’Vesharronne , Jiang Hongfeng , Cremers Serge , Wu Christina , Akashi Hirokazu , Takayama Hiroo , Naka Yoshifumi , George Isaac , Goldberg Ira , Schulze Paul Christian
Published: April 2024

Background:
Advanced heart failure (HF) is associated with myocardial metabolic derangements and insulin resistance. Acylcarnitine (AC) accumulation has been suggested to be a marker of abnormal fatty acid metabolism and mitochondrial dysfunction. We hypothesized that ACs accumulate in the failing myocardium and blood of patients with HF compared to controls.

Methods:
Myocardial and plasma samples were obtained from HF patients during ventricular assist device (VAD) placement and explantation. Control (CON) samples were obtained from hearts not used for heart transplantation. CON plasma was collected from healthy donors. After methanol extraction of total lipids, ACs were measured by LC/MS/MS (MS ACQUITY UPLC).

Results:
Our study included 11 patients with HF (age 61±8 yrs, EF 17±5%, BMI 28±4 kg/m2) before and after LVAD placement and 6 CON (age 41 ±2 yrs, EF>60%, BMI 26±5 kg/m2).

Free carnitine levels decreased in failing myocardium compared to CON (15.7±11.8 vs 16.2±93.0 ng/mg, p<0.001) without plasma changes. Total ACs decreased in failing myocardium compared to CON (45.9±35.9 vs 132.2±94.0 ng/mg, p<0.01). Of note, the cardiac AC/carnitine ratio was higher in HF compared to CON (387% of con, p<0.001) and remained unchanged post-VAD.

Circulating total AC levels were higher in HF compared to CON (7.7±2.8 vs 4.7±2.7 ng/ml, p<0.05) with a decrease post-VAD (5.7±1.6 ng/ml, p<0.05 vs pre-VAD). Short chain (C2+C3), medium chain (C4-C12) and long chain ACs (C14-C18) were found increased in HF plasma (+162%, +158% and +174% vs CON, respectively; all p<0.05) with subsequent decrease post-VAD (-73%, -66% and -81% vs pre-VAD, respectively; all p<0.05). The circulating total AC/free carnitine ratio trended to be higher in HF (1.0±0.3 vs 0.7±0.4 in CON, p=0.1) without changes post-VAD.

Conclusion:
Metabolic derangements in HF include changes in circulating and cardiac ACs with a distinct response to mechanical unloading. An increased ACs/carnitine ratio suggests impaired fatty acid metabolism and mitochondrial dysfunction leading to accumulation of ACs in the failing myocardium. These novel findings implicate abnormal AC metabolism in the metabolic abnormalities and insulin resistance of patients with advanced HF.
Abstract 18834: Right Ventricular Fractional Area Change Obtained in Different Echocardiographic Views of Right Heart; Comparison With Right Ventricular Ejection Fraction by Cardiac Magnetic Resonance Imaging
Authors: Takemoto Rika , Oe Hiroki , Ugawa Satoko , Toh Norihisa , Watanabe Nobuhisa , Tanabe Yasuharu , Ito Hiroshi
Published: April 2024

Background and Purpose:
Fractional area change(FAC) has been shown to correlate well with right ventricular(RV) ejection fraction(EF) by cardiac magnetic resonance(CMR). The guideline recommends that multiple echocardiographic views should be obtained to evaluate RV function. However, there is no clear recommendation which view should be used to evaluate RV FAC.

Methods:
CMR and transthoracic echocardiography(TTE) were performed in 46 consecutive patients for evaluation of RV function. We measured tricuspid annular plain systolic excursion (TAPSE) , FAC on apical four chamber view (A4CV)(A-FAC) and that of RV focused A4CV (F-FAC) and modified A4CV (M-FAC) and pulsed Doppler peak velocity at the tricuspid annulus (s’) as an assessment of RV systolic function. The association between echocardiography-derived parameters of RV systolic function and CMR-derived measurement of RVEF and RV volume were evaluated.

Result:
Both A-FAC and F-FAC measurement were fesible in 46 patients (100%) and M-FAC measurement was fesible in 39 patients (85%). End diastolic area (Area ED)(cm2) of A-FAC and F-FAC showed correlation with CMR-derived end diastolic volume, respectively (p<0.0001, r=0.66 vs P=<0.0001,r=0.62 ). End systolic area (Area ES)(cm2) of A-FAC and F-FAC showed correlation with CMR-derived end systolic volume, respectively (p<0.0001, r=0.72 vs p<0.0001, r=0.78) P=<0.0001,r=0.65). A-FAC and F-FAC has good correlation with CMR-derived RVEF(p=0.0003, r=0.50 vs P=<0.0001,r=0.65, respectively). M-FAC has no correlation with CMR-derived RVEF(p=0.065, r=0.30). There were no significant agreement between TAPSE, s’ and CMR-derived RVEF in this study.

Conclusion:
Both A-FAC and F-FAC had good correlation with CMR-derived RVEF, and M-FAC didn’t show correlation with CMR-derived RVEF.
Abstract 18867: High Density Electrical Mapping With Conformal Electrode Arrays
Authors: Ptaszek Leon , Ghaffari Roozbeh , Liu Cliff , Quivira Fernando , Heist E Kevin , Klinker Lauren , Work John , Hsu Yung-Yu , Lee Stephen , Su Garren , Cordaro Kevin , Ruskin Jeremy N , Mansour Moussa
Published: April 2024

Introduction:
High-resolution mapping catheters could facilitate detailed mapping of complex arrhythmias, such as persistent atrial fibrillation (AF). Detailed map information acquired with a high-resolution catheter could potentially improve the efficacy of ablation. The goal of this study was to test the feasibility of cardiac mapping using a catheter-based conformal high-density (HD) electrode array (16 electrodes/cm2) that significantly enhances spatial mapping resolution relative to existing devices.

Methods:
In vivo studies of the catheter-based HD electrode arrays were performed in 4 swine. The HD array was embedded in the balloon and was used to measure atrial electrical activity during both sinus rhythm (SR) and pacing-induced AF. Signal fidelity was evaluated during maneuvers of the catheter in the atria.

Results:
Activation patterns were identified and propagation speeds were characterized during sinus rhythm and pacing-induced AF. These HD recordings were then used to generate iso-potential conduction maps (Figure).

Conclusions:
Electrogram measurement with the HD conformal electrode array was feasible, and enabled fine spatio-temporal mapping of the atria during SR and AF, and has the potential to help better define the arrhythmogenic substrate(s) of complex arrhythmias.
Abstract 18873: Protection of CD39 Transgenic Mice From Cerebral Ischemic Injury
Authors: Baek Amy , Petrovic-Djergovic Danica , Liao Hui , Ray Jessica , Sutton Nadia , Kanthi Yogendra , Pinsky David
Published: April 2024

Cerebral tissue damage after an ischemic event can be exacerbated by inflammation and thrombosis. Elevated levels of extracellular ATP and ADP are associated with cellular injury and promote inflammation and thrombosis. Ectonucleoside triphosphate diphosphohydrolase 1 (CD39), an enzyme expressed on the plasmalemma of leukocytes and endothelial cells, suppresses platelet activation and leukocyte infiltration by phosphohydrolyzing ATP and ADP.

To investigate the effects of increased CD39 in an in vivo model of cerebral ischemia, we developed a transgenic mouse expressing human CD39 (hCD39). A floxed stop sequence was inserted prior to the transcriptional start site of hCD39, generating a mouse in which the expression of hCD39 can be controlled in a tissue-specific manner with specific Cre recombinase mice. Here, we generated mice that express hCD39 globally, using an EIIA-Cre mouse. Bone marrow analysis showed similar endogenous CD39 mRNA between transgenic (TG) and wild type (WT) mice while expression of the human transgene was >3,600-fold greater than the mouse gene (p<0.0001, n=3). Cerebral ischemia was induced using a photothrombotic model of middle cerebral artery (MCA) occlusion, which is clinically relevant to ischemic stroke. After 48 hours, mice underwent brain MRI and infarct volumes were quantified. TG hCD39 mice had 37.8% smaller infarct volumes (p<0.05, n=5). A second cohort of mice was assessed for neurological deficits - TG mice showed lower deficits compared to WT (1.0 vs 1.5 based on an established 5-point scale p<0.02, n=8). Western blot analysis of non-ischemic hemispheres showed that TG mice had significantly more CD39 expression than WT mice (5.4-fold, n=3, p<0.0001) Leukocytes from ischemic and contralateral hemispheres were purified for flow cytometric analysis. While contralateral hemispheres had the same numbers of macrophages and neutrophils (CD45+/ F4/80+ and CD45+/Ly6g+ respectively), ischemic hemispheres from TG mice had 64% fewer infiltrating macrophages and 68% fewer neutrophils (p<0.001, n=8).

This is the first report of transgenic overexpression of CD39 in mice imparting a protective phenotype following stroke, with reduced leukocyte infiltration, smaller infarct volumes and decreased neurological deficit.
Abstract 18911: Prognosis of Latent Systolic Dysfunction in Patients Referred for Stress Echocardiography With Normal LV Ejection Fraction
Authors: Supariwala Azhar A , Gonzales Waddy , Pierce Matthew , Kahan Jonathan , Thammaiah Yathin , Sangli Swathi , Duttuluri Manideep , Pai Poonam , Chaudhry Farooq A
Published: April 2024

Background:
Tissue Doppler imaging can assess latent systolic function. The prognostic impact of latent systolic dysfunction in patients with normal ejection fraction is limited.

Methods:
We measured the left ventricular septal S wave velocity (Sm) at rest in 908 patients, mean age 58 ±14 years, 40% males who were referred for stress echocardiography with normal left ventricular ejection fraction (>55%).

Results:
There were 42 (5%) deaths during the mean follow-up of 3.1 ± 0.6 years. Only 44 (6%) had ischemia on stress echocardiogram. There were significant high correlations observed between age and Sm and E′ (r= -0.24; p<0.001 and r= -0.53; p<0.001, respectively) and very high correlations were observed between Sm and E′ (r =0.51; p<0.001). After adjusting for age, gender, CAD risk factors, and ischemia, and interaction of age*Sm, higher age (HR=1.01; 95% CI: 1.004 - 1.01; p<0.001) with normal S wave velocity, and higher S wave velocity (HR = 0.51; 95% CI: 0.36 - 0.73; p<0.001) independent of age were the predictors of mortality. Similarly, diastolic dysfunction was a predictor of mortality (HR= 0.56; 95% CI = 0.41 - 0.76; p<0.001). [FIGURE] However, addition of Sm in the model after E′ or addition of E′ after Sm does not affect the model. On sub-group analyses, taking only patients with diastolic dysfunction same results were observed. Lower Sm and E′ septal both were predictors of worse outcomes but dependent on each other.

Conclusion:
Latent systolic dysfunction and diastolic dysfunction are highly correlated and associated with worse outcomes in patients with normal ejection fraction. Further studies with large cohort and longer follow-up are needed to determine whether these basic indices can prognosticate this cohort.
Abstract 18928: Vorapaxar Reduces Coronary Stent Thrombosis: Results From the TRA2P-TIMI 50 Trial
Authors: Bonaca Marc P , Scirica Benjamin M , Braunwald Eugene , Wiviott Stephen D , Murphy Sabina A , Morrow David A
Published: April 2024

BACKGROUND:
Vorapaxar is a novel potent antiplatelet agent that reduces cardiovascular death and recurrent thrombotic events when added to standard antiplatelet therapy. We investigated whether treatment with vorapaxar reduced the rate of coronary stent thrombosis (ST) in stable patients with atherosclerotic vascular disease.

METHODS:
TRA2°P-TIMI 50 was a multinational, randomized, double-blind, placebo controlled trial of vorapaxar in stable patients with prior MI, peripheral arterial disease, or stroke. We evaluated the rates of definite ST as adjudicated by a central events committee using Academic Research Consortium (ARC) criteria.

RESULTS:
A total of 26,449 patients were randomized with 14,042 (53%) having a history of a coronary stent implantation prior to randomization. An additional 449 patients received a coronary stent during the trial. The rate of ARC definite stent thrombosis in placebo group at three years was 1.4% (0.47% per year) in those with a coronary stent implanted prior to or during the trial (Fig 1A). Vorapaxar reduced ARC definite ST (1.1% at three years, 0.36% per year, HR 0.71, p=0.040, figure 1B). In those patients who qualified for the trial with MI (17,779, 77% on aspirin and thienopyridine), 76% had a history of prior stenting or a new stent during the trial (13,489). The rate of ST was similar (0.47% per year placebo, Fig 1A) with a consistent reduction with vorapaxar (HR 0.71, p=0.046, Fig 1B).

CONCLUSIONS:
The rate of ARC definite ST in stable patients with coronary stents, the majority of whom were receiving DAPT, was approximately 1.4% at three years. Vorapaxar significantly reduced ARC definite ST in stable patients with atherosclerotic vascular disease and history of coronary stent on standard antiplatelet therapy.
Abstract 18931: The Effect of Breaking Advanced Glycation End-Products, With or Without Exercise Training on the Cardiovascular Effects of Aging
Authors: Howden Erin , Sander-Oudegeest Madelijn , Carrick-Ranson Graeme , Sarma Tom , Fujimoto Naoki , Shibata Shige , Palmer Dean , Boyd Kara , van Dijk Arie , Hopman Maria , Levine Benjamin
Published: April 2024

Introduction:
Sedentary aging impairs cardiovascular (CV) structure and function. Lifelong exercise training maintains youthful left ventricular (LV) and vascular structure but has little effect on relaxation. Moreover, exercise has no effect on CV structure when begun later in life, perhaps because of the accumulation of advanced glvcation end-products (AGE). Alagebrium is a crosslink breaker that improves LV compliance in older animals, especially when combined with exercise training. We hypothesised that exercise combined with Alagebrium would improve LV function in sedentary humans.

Methods:
This was a dual-centre double-blind placebo controlled randomized trial with a 1-year intervention. We recruited 110 healthy subjects from the Dallas, TX (n=62) and Nijmegen, Netherlands (n=48). Subjects were randomized to either: a) no exercise+placebo; b) no exercise+Alagebrium [200mg/day]; c) Exercise+placebo; and d) Exercise+Alagebrium. We measured (VO
2
max) and used 2-D echo for measurement of speckle tracking imaging (global longitudinal strain [GLS], systolic strain rate [SR], early diastolic strain rate [SR] and late diastolic strain rate [AR]).

Results:
Ninety-nine subjects (age 68±5yrs; 53f/46m) completed the 1-year intervention. There were no group differences at baseline for VO
2
max, GLS, SR, ER or AR. Exercise training increased VO
2
max (
P
<0.001) without an additive effect of drug (
P
=0.79). There was no effect of drug, training, or any combination on GLS (
P
values ranged from 0.24-0.57), SR (
P
=0.77- 0.91), ER (
P
=0.37- 0.63), AR (
P
=0.09 - 0.20) [Table 1].

Conclusion:
One-year of exercise training, AGE cross link inhibition or their combination does not significantly improve LV function measured by speckle tracking in previously sedentary seniors.
Abstract 18939: Trends in Antithrombotic Therapy for Atrial Fibrillation in the Veterans Affairs
Authors: Vaughan Sarrazin Mary , Cram Pete , Kaboli Peter
Published: April 2024

INTRODUCTION:
The CHADS2 is a stroke risk score developed in 2001 to guide the selection of antithrombotic therapy for patients with atrial fibrillation (AF). Since 2001 the CHADS2 has been adopted into multiple practice guidelines. Anticoagulation by warfarin or newer anticoagulants is recommended for patients with CHADS2 of 2 or higher, with aspirin or clopidogrel recommended for lower CHADS2 scores. We evaluated trends during 2002-2011 in antithrombotic therapy by CHADS2 score for patients with new AF episodes in the Veterans Affairs (VA).

METHODS:
New AF episodes were defined by at least two encounters for AF (ICD-9-CM 427.31) and no previous AF episodes based on national VA data (n=297,611). Patient age and diagnoses for hypertension, diabetes, heart failure, and stroke during the 12 months preceding AF were used to calculate CHADS2 scores. Receipt of warfarin, dabigatran, or clopidogrel within 90 days of the AF episode was identified in VA national pharmacy data. Trends in antithrombotic therapy by CHADS2 score were examined in unadjusted analyses and in analyses that controlled for bleeding risk.

RESULTS:
Overall, 54% of patients received antithrombotics within 90 days of AF. Among those, 88% received warfarin and 18% received clopidogrel. Dabigatran (available in the VA in 2011) accounted for 0.4% of patients in 2010-2011. From 2002 through 2011, the proportion of patients prescribed warfarin within 90 days of AF decreased by 26%, 23%, 15%, 13%, 8%, and 10%, for patients with CHADS2 score of 0, 1, 2, 3, 4, and 5-6, respectively (p<.0010).

Clopidogrel use decreased by 17% and 20% over the 10-year period for patients with CHADS2 of 1 or 5 or more, respectively, but increased for patients with CHADS2 of 1, 2, or 3. Results were similar controlling for bleeding risk factors.

LIMITATIONS:
We were unable to assess the use of aspirin due to its availability without a prescription.

CONCLUSIONS:
Widespread adoption of the CHADS2 stroke risk score in practice guidelines appears to have impacted anticoagulation prescribing patterns for warfarin. Results for clopidogrel were mixed, likely due to the use of clopidogrel for other cardiac conditions. The overall decline in antithrombotic agents in our study, even among patients with high CHADS, warrants investigation.
Abstract 18942: Coronary CT Angiography versus Stress Imaging for Initial Risk Stratification (CT-FIRST): A Randomized Prospective Trial on Downstream Resource Utilization
Authors: Villines Todd C , Gore Rosco , Bindeman Jody , Cheezum Michael , Nguyen Binh , Devine Patrick J , Taylor Allen J
Published: April 2024

Introduction:
Noninvasive stress myocardial imaging studies are commonly utilized to evaluate patients with chest pain. While coronary computed tomographic angiography (CTA) is highly accurate for the diagnosis of coronary artery disease (CAD), its comparative effectiveness versus stress imaging on downstream resource utilization is undefined.

Hypothesis:
We assessed the hypothesis that coronary CTA may be associated with lower downstream resource utilization as compared to stress imaging.

Methods:
We randomized 240 adults without prior CAD who were clinically referred for stress imaging (single photon emission computed tomography [SPECT] or stress echocardiography) to subsequent 64-slice CTA versus stress imaging alone (1:1). CTA readers were blinded to clinical and stress test results and patients were prospectively followed over 24 months for the primary outcome of mean per-patient downstream clinical evaluations and additional cardiac testing (composite) for the initial anginal complaint.

Results:
Patient were of mean age 52 ± 9 years (58% male) with mean pre-test probability (Diamond-Forrester) of 44 ± 20%. Most (67%) underwent SPECT (86% exercise), with 37% undergoing exercise stress echocardiography. Stress imaging studies demonstrated ischemia in 5% of subjects. Coronary CTA was normal in 52% with 40%, 5% and 1% having mild (<50%), moderate (50-69%) and severe (>70%) stenosis, respectively. Most patients (67%) underwent no further posttest evaluation. Coronary CTA was associated with significantly fewer total downstream encounters (0.4; 95% CI -0.5-1.4) versus no CTA (1.3; 0.9-1.6; p=0.02) and fewer clinic and emergency room visits per-subject (0.29 vs. 1.03; p=0.04). Downstream stress tests, catheterizations, revascularizations and acute coronary events were similar between groups. Discrepancies between CTA and stress imaging were rare (3 abnormal SPECT with normal CTA) and 9% of CTA patients required follow-up for incidental findings. There were no significant differences in aspirin or statin medication utilization.

Conclusions:
Among a stable symptomatic cohort with low CAD prevalence undergoing stress imaging, coronary CTA was associated with incrementally lower rates of downstream clinical evaluations.
Abstract 18945: miR-208a-3p is Downregulated in Cardiac Remodeling and Possibly Controls Gata4 Expression
Authors: Farjun Bruna , Barbosa Raiana A , Alves Leonardo M , Suhett Grazielle D , Pinto Leonardo M , Paula Luis Felipe S , Brasil Guilherme V , Carvalho Alysson R , Nascimento Jose H , Carvalho Adriana B
Published: April 2024

miR-208a-3p, a cardiac specific microRNA encoded by an intron of the α-myosin heavy chain (α-MHC) gene, is a predicted post-transcriptional repressor of Gata4. Hence, the aim of this work was to correlate the temporal expression profile of miR-208a-3p and Gata4 in cardiac remodeling after myocardial infarction (MI). Wistar rats were submitted to permanent occlusion (PO) of the left anterior descending artery and analyzes were performed in SHAM and MI groups with 2 (n=10 e n=7), 28 (n=8 e n=9) and 90 days post-PO (n=8 e n=9). Cardiac function was examined by echocardiography and Langendorff, while infarct area was obtained from histological analyzes. The relative expression of miR-208a-3p, α-MHC and Gata4 were obtained by RT-qPCR. There were no differences in infarct areas between infarcted animals in all timepoints and functional data were consistent with dilated cardiomyopathy. The relative expression of miR-208a-3p was downregulated both 2 days post-PO (0.12 ± 1.52 p<0.01) and 90 days post-OP (0.18 ± 1.78, p<0.01) in the MI group when compared to SHAM. mRNA levels of α-MHC and Gata4 were also decreased in the MI group at the same times post-PO (α-MHC 2 days: 0.004 ± 6.98, 90 days: 0.05 ± 3.42; Gata4 2 days: 0.25 ±1.54, 90 days: 0.24 ± 3.01). Pearson’s correlation coefficient revealed the existence of a linear correlation between the mRNA levels of Gata4 and α-MHC at 2 days (p=0.0003, R2=0.78) and 90 days post-PO (p<0.0001, R2=0.86). Moreover, the correlation between Gata4 expression and miR-208a-3p was also present at 2 days (p=0.009, R2=0.54) and 90 days post-PO (p=0.04, R2=0.34), as well between α-MHC e miR-208a-3p at 2 days post-PO (p=0.01, R2=0.49). Since miR-208a-3p is coexpressed with α-MHC, which is a direct target of Gata4, we propose that miR-208a-3p decreases Gata4 expression through negative feedback loop. In this context, miR-208a-3p would function as a rheostat, regulating the levels of Gata4.
Abstract 18947: Clonal C-kit-Positive Bone Marrow Cells and Cardiomyogenesis
Authors: Sanada Fumihiro , Kim Junghyun , Czarna Anna , Signore Sergio , Sorrentino Andrea , Mangiaracina Chiara , Kannappan Ramaswamy , Goihberg Polina , Rota Marcello , Hosoda Toru , Kajstura Jan , Anversa Piero , Leri Annarosa
Published: April 2024

Conflicting results have been reported concerning the ability of c-kit-positive bone marrow cells (c-kit-BMCs) to transdifferentiate into cardiomyocytes. We have raised the possibility that c-kit-BMCs may constitute a functionally heterogeneous pool, containing cells with different cardiomyogenic potential. To test this hypothesis, multicellular clones derived from individual c-kit-BMCs were obtained and transplanted in acutely infarcted mice. Only a limited fraction of clonal c-kit-BMCs was found to be able to form cardiomyocytes and promote myocardial regeneration. On this basis, c-kit-BMC-derived clones were classified as myogenic or non-myogenic. The gene profile of these two categories of cells was studied by RNA-sequencing. Genes that showed a significant (p<0.05) expression difference among cell groups were included in the analysis; 35 genes were uniquely upregulated in myogenic c-kit-BMCs. These results were subjected to functional annotation using gene ontology for the identification of molecular pathways showing different state of activation or repression in myogenic c-kit-BMCs. The 35 upregulated transcripts in myogenic c-kit-BMCs involved signal transduction and cell differentiation pathways. Similarly, a set of genes implicated in the response to stress were more represented in myogenic c-kit-BMCs, possibly reflecting the proficiency of this cell class to engraft in the microenvironment of the infarcted heart. A subset of these genes was found to be highly expressed in adult c-kit-positive resident cardiac stem cells. They included sequestosome1 and phosphodiesterase1C, which are highly expressed during cardiac development. Moreover, cathepsin D, which favors angiotensin II formation, sarcomeric accumulation, and myocyte hypertrophy, was more represented in myogenic c-kit-BMCs. With respect to the whole pool of freshly isolated c-kit-BMCs, 105 genes were downregulated in myogenic c-kit-BMCs, indicating that transdifferentation into cardiomyocytes requires the suppression of hematopoietic factors. In conclusion, c-kit-BMCs are functionally heterogeneous, containing cells with different cardiomyogenic potential.