bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 9718: Risk Factors for the Development and Progression of Thoracic Aorta Calcification: The Multi-Ethnic Study of Atherosclerosis (MESA)
Authors: Youssef George , Guo Mengye , Kronmal Richard , McClelland Robyn L , Shavelle David M , Nasir Khurram , Rivera Juan , Carr J. Jeffrey , Wong Nathan D , Budoff Matthew
Published: April 2024

Objective:
To evaluate risk factors for the incidence and progression of thoracic aorta calcification (TAC)

Introduction
: Vascular calcification independently predicts cardiovascular disease (CVD) and computed tomography (CT) is a useful tool to evaluate and quantify TAC. Previous TAC progression reports were limited to dialysis and renal transplant patients, This is the first study to evaluate TAC progression in a large multi-ethnic cohort without clinically evident CVD at entry

Methods:
Non-contrast enhanced cardiac CT (EBCT or MSCT) were obtained in 5886 of the 6814 MESA participants (mean age 62 yrs; 48% male; 40% white, 27% African American (AA), 21% Hispanic, 12% Chinese. Baseline (BL) and follow up (FU) TAC scores were derived

Results:
4308 (73%) subjects had no detectable BL TAC. Mean FU duration was 2.4±0.8 yrs, during which 12% developed TAC. The overall incidence rate was 4.8%/yr and was greater with age across gender and ethnic groups,TAC incidence was significantly lower in AA than whites. Regression analyses showed FU time, age, systolic BP, antihypertensives, and smoking were predictors of incident TAC. 1578 (27%) subjects had prevalent TAC at BL scan with a positive association between the averaged annual TAC change and BL age. While the overall median (25
th
, 75
th
%tiles) change was 32.9 (-1.4,112.2) Agatston units, 38% of study population showed an annual Agatston score progression change of 10-99 and AA showed the lowest median across all ethnic groups; 22.7 (-3,86.8). Regression analyses showed MSCT use, FU time, age, systolic BP, lipid-lowering medication, DM and current smoking were predictors of TAC progression (Tab1)

Conclusion:
In the MESA cohort, both TAC incidence and progression were significantly associated with traditional CV risk factors. AA had the lowest incidence and median change across ethnic groups, consistent with previous findings for coronary calcification. Further studies are needed to correlate progression with outcome data
Abstract 9721: Clinical Significance of Transthoracic Doppler Echocardiography in Patients With a Proximal Left Coronary Artery Lesion That Could Not be Evaluated With Computed Tomography Angiography
Authors: Saito Makoto , Okayama Hideki , Higashi Haruhiko , Morioka Hiroe , Aono Jun , Yoshii Toyofumi , Sumimoto Takumi , Nishimura Kazuhisa , Inoue Katsuji , Higaki Jitsuo
Published: April 2024

Background
The aim of this study was to evaluate the clinical significance of transthoracic Doppler echocardiography (TTDE) in patients with suspected angina pectoris (AP), who had a proximal left anterior descending coronary artery (LAD) lesion that was difficult to evaluate with computed tomography coronary angiography (CTCA).

Methods
Among 387 consecutive patients with suspected AP who had CTCA performed, 58 had a proximal LAD lesion that was difficult to evaluate and were included in this study. These patients had TTDE and coronary angiography performed on the same day (mean age, 74±8 yrs; men, 39; Agaston score, 1110 ± 1360). Proximal left coronary flow was measured in the short axis (SAX) at the aortic root using color Doppler guidance. When coronary flow showed color aliasing, the color velocity range was gradually increased until color aliasing nearly disappeared. When color aliasing did not disappear, the color baseline was shifted until the color flow showed “isovelocity”. Using QCA-CMS analytical software, severe and moderate stenoses were defined as a %diameter stenosis > than 70% and 40-70%, respectively.

Results
Proximal coronary flow was detected in 45 of 58 patients. In these 45 patients, there were 5 patients with severe stenosis and 14 patients with moderate stenosis. The isovelocity in the two groups with stenosis was significantly higher than that in the group without stenosis (148±42 vs 97±48 vs 41±21 cm/s, p<0.001). ROC curve analysis showed that the optimal cut-off values of isovelocity to detect severe and moderate stenoses were > 92 cm/s (area under the curve, 0.96; sensitivity, 100%; specificity, 90%) and > 57 cm/s (area under curve, 0.92; sensitivity, 90%; specificity, 77%).

Conclusion
TTDE could evaluate proximal LAD stenosis with good accuracy in about 80% patients with AP, who had a proximal LAD that could not be evaluated with CTCA. This method may play a complementary role to identify latent proximal LAD stenosis.
Abstract 9726: Prolonged Insulin Secretion After Oral Glucose Load is Associated With Severity of Coronary Artery Disease
Authors: Murata Makoto , Adachi Hitoshi , Takama Noriaki , Sawada Yusuke , Masuda Kuniko , Kurosawa Kohji , Funada Ryuichi , Seki Ryotaro , Kawaguchi Ren , Toyama Takuji , Hoshizaki Hiroshi , Ohshima Shigeru , Kurabayashi Masahiko ,   Gunma Prefectual Cardiovascular Cntr,Cardiovascular Team
Published: April 2024

Introduction:
Hyperglycemia exerts its direct detrimental effects toward the progression of atherosclerosis. However, the role of hyperinsulinemia in the development of atherosclerosis remains to be determined. Little is known about the relationship between cardiovascular events and plasma insulin levels. Hypothesis: We

hypothesize that hyperinsulinemia is associated with the severity of coronary atherosclerosis.

Methods:
Three hundred and forty four consecutive patients (mean age 63±14 SD years; 272 male patients, 72 female patients) who underwent coronary angiography and 2-h 75-g oral glucose tolerance test (OGTT) from April 2006 to January 2012 were enrolled. We excluded the patients with left main trunk lesion, or prior diagnosed diabetes. Based on the number of stenotic vessels, the patients were classified into 4 groups; 0 vessel disease (VD) (n=35), 1VD (n=142), 2VD (n=92), and 3VD (n=36). We measured plasma glucose and insulin levels after 75-g oral glucose load.

Results:
Baseline characteristics were similar among the 4 groups with respect to age, gender, medications, and each of major coronary risk factors. There were no differences glucose profiles in 75-g OGTT, homeostasis model assessment-insulin resistance (HOMA-IR), HOMA-β and HbA1c among these groups (Figure 1A). However, insulin secretion was higher in 2VD and 3VD groups at 120 min whereas no significant difference in insulin secretion at 0, 30 and 60 min (Figure 1B). Furthermore, insulinogenic index at 120 min was increased in 2VD (1.21±1.05[p<0.001]) and 3VD (1.14±0.5l[p=0.002]) compared with 0VD despite of no significant difference in common insulinogenic index.

Conclusions:
Despite no significant difference in insulin resistance and postprandial hyperglycemia prolonged insulin secretion was associated with multivessel coronary artery disease. Prolonged postprandial hyperinsulinemia may promote progression of atherosclerosis.
Abstract 9728: The Timing of Valve Repair for Severe Degenerative Mitral Regurgitation and the Long-term Left Ventricular Function
Authors: Kitai Takeshi , Okada Yukikatsu , Tani Tomoko , Kaji Shuichiro , Yamamuro Atsushi , Ehara Natsuhiko , Kim Kitae , Kinoshita Makoto , Kita Toru , Furukawa Yutaka
Published: April 2024

Background:
The current ACC/AHA guideline recommends early mitral valve (MV) repair for asymptomatic severe mitral regurgitation (MR) in the absence of left ventricular (LV) dysfunction. However, the effects of early MV repair on the long-term LV function and the threshold of the preoperative parameters to maintain favorable long-term LV function have not been clarified. This study aimed to evaluate the incidence and predictors of postoperative LV dysfunction as well as the clinical outcomes.

Methods:
A total of 908 patients who underwent MV repair for severe degenerative MR in our institution between 1996 and 2010 were retrospectively reviewed. Among them, both preoperative and 3-year postoperative echocardiographic data were available in 437 patients. Pre- and postoperative echocardiographic data and clinical outcomes were evaluated.

Results:
Receiver-operating characteristics curve analysis identified preoperative LV ejection fraction (EF) >65% (area under curve (AUC), 0.65; P<0.001) and LV end-systolic dimension (ESD) <38 mm (AUC, 0.68; P<0.001) as cut off values for predicting LVEF ≥60% 3 years after surgery. Patients were divided into 2 groups according to the preoperative LV measures; group A (n=193), LVEF >65% and LVESD <38mm and group B (n=280), LVEF ≤65% and/or LVESD ≥38mm. There were significantly higher rates of postoperative LV dysfunction in group B (A vs B, 24% vs 49%, P<0.001). Moreover, the 10-year event-free survival rate, defined as a composite of death, hospitalization because of heart failure, and recurrent MR was significantly lower in group B than those in group A (A vs B, 86% vs 70%, P=0.02). Among patients in group A, preoperative LVESD was the only independent predictor of postoperative LV dysfunction.

Conclusion:
Simple preoperative echocardiography measures allow the prediction of postoperative LV dysfunction. Patients with preoperative LVEF >65% and LVESD <38 mm may offer better long-term postoperative LV function.
Abstract 9755: Bleeding Complications During Long-term Dual Antiplatelet Treatment In Diabetic Patients Treated With 1
St
Generation Drug Eluting Stent Implantation
Authors: Voudris Vassilis , Karyofillis Panagiotis , Doulaptsis Constantinos , Moukas Ioannis , Thomopoulou Sophia , Cokkinos Dennis V
Published: April 2024

Background:
Dual antiplatelet treatment (DAPLT) for at least 12 months is recommended after drug-eluting stent (DES) implantation. We investigate the frequency, correlates, and clinical significance of bleeding complications in diabetic patients (pts) on long-term DAPLT (5 years) after 1
st
generation DES implantation.

Methods:
We assessed 610 consecutive diabetes mellitus (DM) pts (male 80%, mean age 65±9 years) after 1
st
generation DES implantation (sirolimus 80%, paclitaxel 10%, combination 10%). Five years clinical follow-up (FU), obtained in 587/610 (96%) of them; at the end of FU, 211(36%) pts were on single APLT (SAPLT) and 376 (64%) on DAPLT. Bleeding complications were defined according to PLATO and TIMI definitions. Hard end-point (HEP) was considered the combination of death, non-fatal myocardial infarction, and cerebrovascular accident; stent thrombosis (ST) is assessed according to ARC definition.

Results:
There was no difference in the incidence of ST and HEP in pts treated with DAPLT vs. SAPLT. The incidence of bleeding was higher on DAPLT pts (14.6% vs 3.8%, p < 0.0001). Minor bleeding according to PLATO occurred in 1.9% of pts on SAPLT and 11.7% on DAPLT (p<0.0001) and according to TIMI in 2.4% vs. 13.6% respectively (p< 0.0001). Major bleeding according to PLATO presented the 1.9% of pts on SAPLT and 2.9% on DAPLT (p: NS); according to TIMI the incidence of major bleeding was 1.4% and 1.1% respectively (p: NS). The incidence of cardiovascular adverse events was similar between pts with bleeding as compared with those without bleeding. In a multivariable analysis, smoking was an independent predictor for overall as well as major bleeding according to PLATO (HR 6.2, 95% CI 1.2-30.4, p=0.024), whereas DAPLT was an independent predictor for overall and minor bleeding (HR 6.2, 95% CI 2.2-17.3, p<0.0001)

Conclusions:
Long-term DAPLT in DM pts treated with 1
st
generation DES is associated with higher risk of overall and minor but not major bleeding. Smoking was an independent predictor for overall and major bleeding according to PLATO definitions.
Abstract 9792: Chrontropic Incompetence in Heart Failure and the Relationship of Minute Ventilation and Chronotropic Response During Exercise
Authors: Hopper Donald L , Abraham JoEllyn M , Samara Michael A , Wilkoff Bruce
Published: April 2024

BACKGROUND: Cardiac pulmonary mismatch is prevalent in heart failure patients that exhibit chronotropic incompetence (CI). Wilkoff’s model provides evaluation of metabolic chronotropic response (MCR) during exercise. In addition to CI we evaluated a new measure of the normalized heart rate to normalized minute ventilation relationship during exercise (HRn/VEn) which,in combination with the MCR slope, may provide discriminating information in regards to identifying those normal subjects and heart failure patients who would most likely benefit from adaptive rate pacing. Normalization allows comparison of subjects and identification of patients with CI regardless of Age, functional capacity, and during submaximal workloads.

METHOD: We studied the resulting MCR slopes and the HRn/VEn slopes in 40 normal subjects (N) (age 37±9) and 40 heart failure patients (HF) implanted with BiV CRT-D devices (age 62±9) during graded exercise testing by using standard cardiopulmonary exercise testing techniques. Exercise tests were performed to peak exercise (as quantified by the respiratory exchange ratio (RER) RER = 1.13±0.09 N and 1.11±0.07 HF) and the end stage heart rate and minute ventilation data was used in the calculations of the MCR slope and HRn/VEn slopes. RESULTS: Mean MCR slopes were 1.0±0.14 (N) and 0.52±0.23 (HF). The mean HRn/VEn slope were 1.34±0.26 (N) and 0.66±0.28 (HF). Details are presented in the table.

DISSCUSION/CONCLUSSION: When CI is present there is also a significant derangement in the heart rate to pulmonary relationship as shown by the HRn/VEn slopes. A MCR slope of 0.7 which is considered to be severely CI corresponds to a decreased HRn/VEn slope of 0.881 (95% confidence interval of the normal relationship). HF CI patients (MCR slopes <0.7) also exhibit low HRn/VEn measures (> 2 standard deviations from the mean of normal group).
Abstract 9795: Shifting Trends in Incidence and Mortality from Infective Endocarditis Among Medicare Beneficiaries
Authors: Bikdeli Behnood , Wang Yun , Kim Nancy , Desai Mayur , Quagliarello Vincent , Krumholz Harlan M
Published: April 2024

Background:
Infective endocarditis (IE) is the most serious cardiovascular infection in adults. The AHA guidelines in 2007 narrowed the indications for antibiotic prophylaxis for IE. Yet, little is known about recent IE trends among older adults (age≥65 years), who are a growing at-risk population in the United States.

Methods:
We used the Inpatient Medicare standard analytic files to identify 100% of fee-for-service (FFS) patients aged ≥65 with a primary or secondary diagnosis of IE from 1999 to 2010. We built a denominator file from Medicare administrative data to report IE hospitalizations per 100,000 beneficiary-years. Thirty-day and 1-year mortality rates were determined using the vital status files from the Centers for Medicare & Medicaid Services.

Results:
Annually, over 20,000 FFS Medicare beneficiaries were hospitalized with IE. IE incidence was 84 per 100,000 patient-years in 1999, rose gradually to 103 per 100,000 patient years in 2005, and has had a slight decline thereafter (Table 1). From 1999 to 2007, 30-day and 1-year mortality rates remained high, ~15% and ~ 35% respectively. Mortality rates during 2008 were at 16% and 37% respectively; however, risk-adjusted analysis did not show a consistent rise in mortality rates from 2008 onwards.

Conclusion:
Although endocarditis is frequently cited as a rare condition with stable incidence, our findings signify the high burden of IE in older adults. We did not observe a major rise in IE hospitalizations or mortality rates after publication of AHA guidelines in 2007. Our observational study supports the safety of these recommendations.
Abstract 9801: Patient- and Vessel-based SYNTAX Scores by Coronary Computed Tomographic Angiography: A Direct Comparison to Invasive Coronary Angiography
Authors: Shalev Aryeh , Nakazato Ryo , Nakanishi Rine , Arsanjani Reza , Otaki Yuka , Park Hyung Bok , Dey Damini , Gransar Heidi , LaBounty Troy , Cheng Victor , Hayes Sean W , Thomson Louise E , Friedman John D , Berman Daniel S , Min James K
Published: April 2024

Introduction:
The SYNTAX score is commonly used to assess the complexity of coronary artery disease (CAD) by invasive coronary angiography (ICA), and to classify patients at risk for major adverse cardiovascular events following percutaneous coronary intervention. To date, whether the SYNTAX score can be reliably determined from noninvasive coronary CT angiography (CCTA) has not been fully explored.

Hypothesis:
To determine the correlation between global and vessel-specific SYNTAX scores derived from CCTA and ICA.

Methods:
We evaluated 94 consecutive patients (mean age - 66 years, 66% male gender) with and without known CAD, who underwent CCTA and subsequent ICA within 5 days, due to obstructive (>50% stenosis) single-, double-, or triple-vessel CAD. Patients with prior coronary bypass surgery were excluded. Per-patient and per-vessel SYNTAX scores were calculated from CCTA and ICA in blinded fashion by independent and experienced readers. CCTA SYNTAX scores incorporated identical variables as ICA SYNTAX scores. Paired student’s t-test and Spearman’s rank test were employed to determine the relation between CCTA and ICA scores, as well as Bland Altman analysis for agreement.

Results:
On a per-patient basis, obstructive 1-vessel disease (VD), 2-VD and 3-VD was found in 41 (44%), 37 (39%) and 16 (17%) patients, respectively. Left main (LM), left anterior descending (LAD), left circumflex (LCX) and right coronary artery (RCA) obstructive disease was identified in 7 (7%), 69 (73%), 43 (46%) and 47 (50%) patients, respectively. Mean per-patient CCTA and ICA SYNTAX scores were similar (11.2 vs. 11.7, respectively, p=0.07) with excellent correlation and agreement (table). Similar results were observed for per-vessel measures (table).

Conclusion:
Per-patient and per-vessel SYNTAX scores derived from CCTA demonstrate high correlation and agreement to ICA SYNTAX scores. Evaluation of CCTA SYNTAX scores for prediction of pre-ICA risk for MACE now appears warranted.
Abstract 9817: The Changing Practice of Coronary Revascularization of Dialysis Patients in the US, 2004-2009
Authors: Herzog Charles A , Solid Craig A
Published: April 2024

INTRODUCTION:
The optimal method of coronary artery revascularization in dialysis pts is controversial. In-stent restenosis complicates the use of bare metal stents (BMS), prolonged dual anti-platelet therapy (and attendant hemorrhagic risk, including in transplant waitlisted pts) is problematic for drug-eluting stents (DES), and coronary artery bypass surgery (CAB) has markedly increased in-hospital mortality, but superior long-term survival. There are few published data comparing recent trends in selection of coronary revascularization procedures in dialysis pts.

METHODS:
We searched the records of the United States Renal Data System database to identify 23,038 dialysis pts having coronary artery bypass surgery (CAB), BMS or DES in 2004-2009. One year survival was estimated by Kaplan-Meier method.

RESULTS:
During the study period, the total number of revascularization procedures decreased from 4,347 in 2004 to 3,344 in 2009. CAB procedures typically accounted for 25% to 30% of all procedures. From 2004-2006, DES accounted for 59% of procedures and BMS 15%. However, from 2007-2009 those percentages were 43% and 31%, respectively. From 2006 to 2007 alone, the number of DES pts dropped from 2,495 to 1,462 (a 41% reduction) while the number of BMS pts increased from 607 to 1,121 (an 85% increase). Survival for CAB and DES pts, but not BMS improved for 2009 vs 2004 pts (p= .002, p= .015, p= ns, respectively by log rank test).

CONCLUSION:
Our data suggest a recent shift in interventional practice patterns in US dialysis pts, with a reduction in the use of DES. Despite prior reports of superior long-term survival after CAB, only 25% of coronary revascularization was CAB in 2009. Unadjusted survival after DES and CAB improved from 2004 to 2009.
Abstract 9902: Tricuspid Valve Annuloplasty with Edge-to-Edge Repair is Effective Strategy for Management of Functional Tricuspid Regurgitation
Authors: Toyono Manatomo , Navia Jose L , Shiota Takahiro
Published: April 2024

Introduction:
Tricuspid valve (TV) annuloplasty is recommended for management of functional tricuspid regurgitation (TR); however, residual TR occurs up to 25% of patients after surgery. For management of mitral regurgitation, edge-to-edge repair is accepted as effective procedure.

Hypothesis:
TV annuloplasty with edge-to-edge repair is more effective for management of functional TR than isolated TV annuloplasty.

Methods:
We analyzed 216 patients who underwent isolated TV annuloplasty and 75 patients who underwent TV annuloplasty with edge-to-edge repair. Echocardiography was performed to assess response to surgery and cardiac function and geometry 21 ± 5 days before and 6 ± 4 days after surgery. Severity of TR was assessed by maximal jet area in the right atrium. Residual TR was defined as maximal TR jet area >5 cm
2
after surgery.

Results:
There was no significant difference in preoperative functional TR jet area between patients who underwent isolated TV annuloplasty and those who underwent TV annuloplasty with edge-to-edge repair (Table). Patients who underwent isolated TV annuloplasty showed significantly greater TV annulus diameter and lower right ventricular fractional area shortening than those who underwent TV annuloplasty with edge-to-edge repair. In both groups, TR jet area was significantly decreased after surgery. Patients who underwent TV annuloplasty with edge-to-edge repair showed significantly lower postoperative TR jet area as compared with those who underwent isolated TV annuloplasty although mean postoperative TR jet areas were <5 cm
2
in both groups. Patients who underwent TV annuloplasty with edge-to-edge repair showed significantly less residual TR as compared with those who underwent isolated TV annuloplasty.

Conclusions:
TV annuloplasty with edge-to-edge repair is effective procedure for management of functional TR and may be superior to isolated TV annuloplasty.
Abstract 9908: Function and Regulation of the Adipocytokine Ctrp9 in a Mouse Model of Ischemia/reperfusion Injury
Authors: Takahiro Kambara , Ohashi Koji , Shibata Rei , Kataoka Yoshiyuki , Ogura Yasuhiro , Maruyama Sonomi , Enomoto Takashi , Uemura Yusuke , Murohara Toyoaki , Ouchi Noriyuki
Published: April 2024

Background:
Acute coronary syndrome is a leading cause of mortality worldwide. Obesity-related disorders are associated with an increased prevalence of cardiovascular disease as well as an increased cardiac damage after acute coronary syndrome. Although C1q/TNF-related protein (CTRP) 9 is an adipocytokine with beneficial properties for glucose metabolism and endothelial function, nothing is known about the role of CTRP9 in ischemic heart disease. Here we investigated the effect of CTRP9 on acute myocardial injury in a mouse model and examined the regulation of adipocyte CTRP9.

Methods and Results:
Wild-type (WT) mice were subjected to 60 minutes of myocardial ischemia followed by 24 hours of reperfusion. An adenoviral vector expressing CTRP9 (Ad-CTRP9) or β-galactosidase as a control was intravenously injected into WT mice 3 days before surgery. Administration of Ad-CTRP9 reduced infarct size and myocyte apoptosis following myocardial ischemia/reperfusion, which was associated with an elevated phosphorylation of AMP-activated protein kinase (AMPK) in ischemic heart. In cultured cardiac myocytes, treatment with CTRP9 protein attenuated apoptosis during hypoxia/reoxygenation and enhanced AMPK signaling. Meanwhile, inhibition of AMPK activity blocked the anti-apoptotic effect of CTRP9. Plasma CTRP9 levels were reduced in diet-induced obese and genetic obese db/db mice. In addition, myocardial ischemia/reperfusion resulted in a significant reduction of circulating CTRP9 levels with decrease in its expression in adipose tissue. After reperfusion, the expression of inflammatory cytokines and NADPH oxidase components was upregulated in adipose tissue, which was accompanied by increased plasma free fatty acid levels. Treatment of adipocytes with palmitic acid or the inducers of inflammation and oxidative stress reduced CTRP9 expression. Furthermore, systemic delivery of CTRP9 protein at the time of reperfusion attenuated myocardial infarct size in response to ischemia/reperfusion.

Conclusion:
CTRP9 exerts a cardioprotective action during ischemia/reperfusion via AMPK-dependent mechanism. Thus, the enhancement or supplementation of CTRP9 can be novel therapeutic strategies for the treatment of acute coronary syndrome. .
Abstract 9928: Reversal of Anticoagulant Activity of Dabigatran and Dabigatran-induced Bleeding in Rats by a Specific Antidote (Antibody Fragment)
Authors: van Ryn Joanne , Litzenburger Tobias , Schurer Johanna
Published: April 2024

Dabigatran etexilate (DE) is the prodrug of dabigatran, a direct potent thrombin inhibitor, approved as an alternative to warfarin for prevention of strokes in patients with atrial fibrillation. However, as with any anticoagulant, bleeding risks are associated with its use. Though there is no specific antidote available, an antibody fragment (Fab) against dabigatran is currently in development to neutralize its activity. Inhibition of dabigatran and its metabolites was tested in vitro using a diluted thrombin time assay. The ability of the Fab alone to induce coagulation was tested in various assays in human plasma including endogenous thrombin potential (ETP, 5 pM tissue factor) and ecarin chromogenic assay (ECA). Dabigatran etexilate (DE), 30 mg/kg was given orally to rats every 8 hrs to achieve supratherapeutic levels of dabigatran and induce bleeding in a rat tail bleeding model. 45 min after the last dose increasing i.v. Fab doses were given to test for bleeding reversal. Ex vivo clotting and plasma levels of dabigatran and Fab were measured. The Fab potently binds dabigatran (Kd 2 pM). Anticoagulant activity of dabigatran and its metabolites was inhibited with an IC
50
of 3.5 and 2.0 nM in human plasma. Fab had no effect on thrombin generation (ETP, 0.89-fold of control), in contrast FEIBA resulted in ∼2-fold increase in ETP. ECA was not elevated with Fab vs control. DE (30 mg/kg p.o.) was given in 8 hr intervals to achieve steady state levels in the rat, with supratherapeutic plasma levels (1500 nM or ~750 ng/mL). This resulted in ~2-fold increase in tail cut bleeding time. There was a rapid, dose-dependent decrease in blood loss after i.v. injection of Fab, which was maintained for 6 hrs after the highest dose of Fab. aPTT, TT and ECT were all reversed. Treating rats with warfarin (0.5 mg/kg p.o.) over 3 days resulted in a 2-fold elevation of blood loss. Similar doses of Fab had no effect on reversing this elevated blood loss. These data show the specificity and selectivity of the antibody fragment for dabigatran. Administration of the Fab after DE resulted in a safe and rapid reversal of blood loss, which correlated with reversal of ex vivo clotting tests. Thus this agent holds promise for reversing dabigatran-induced anticoagulation and bleeding effects.
Abstract 9944: Temporal Relationship Between Major Hemorrhagic Events and Mortality among Patients with Recent Acute Coronary Syndrome: Insights from ATLAS ACS 2-TIMI 51
Authors: Pride Yuri , Mohanavelu Satishkumar , Mega Jessica , Braunwald Eugene , Gibson C. Michael
Published: April 2024

Background: Multiple studies have demonstrated an association between hemorrhagic events and long-term mortality among patients with ACS. The goals of this analysis were to (1) describe risk factors associated with non-CABG-related TIMI major bleeding and (2) determine whether there was a temporal relationship in the association between hemorrhagic events and mortality.

Methods and results: ATLAS ACS-TIMI 51 enrolled patients with recent ACS and followed them for clinical outcomes for a median of 13 months. Multivariable Cox regression analyses adjusting for treatment and baseline characteristics were used to determine independent risk factors for non-CABG-related TIMI major bleeding. To analyze the hazard ratio and time dependency of bleeding on mortality, we used iterative day-to-day landmark analyses after the hemorrhagic event. Of the 15,526 patients enrolled, 196 (1.26%) had a non-CABG-related TIMI major bleed. Independent predictors of non-CABG-related TIMI major bleeding (p<0.10) included assignment to rivaroxaban, increasing age, male sex, diabetes mellitus, revascularization for the index event and region of enrollment. Non-CABG-related TIMI major bleeding was associated with a significantly increased risk of mortality, even after adjusting for baseline differences (HRadj 5.94, 95% CI 4.2-8.5, p<0.001). However, in the iterative landmark analysis, the hazard ratio did not differ statistically from baseline risk by 12 days after the bleeding event (Figure). Furthermore, in a landmark analysis, there was no difference in mortality among 30-day survivors of major bleeding compared with propensity-matched controls (3.9% vs. 4.1%, p=NS).

Conclusions: Among patients with recent ACS, major bleeding is associated with higher mortality, even after adjusting for differences in baseline characteristics. However, the relationship between major bleeding and mortality is no longer significant 12 days after the bleeding event.
Abstract 9955: Suboptimal Diagnosis and Interventional Treatment of Patients with Bundle Branch Block and Acute Myocardial Infarction
Authors: Sørensen Jacob T , Stengaard Carsten , Sørensen Christina A , Thygesen Kristian A , Bøtker Hans Erik , Thuesen Leif , Terkelsen Christian J
Published: April 2024

Several studies have shown the benefit of rapid revascularization in patients with presumed new-onset bundle branch block myocardial infarction (BBBMI). It is a major challenge to determine the age of the bundle branch block (BBB) and triage accordingly in the acute setting.

Methods
Prehospital ECGs, final diagnosis and mortality were assessed in 4905 consecutive patients with suspected AMI. BBB was defined as QRS duration >120 ms in the absence of pace-rhythm, AV-block or ventricular rhythm. Mortality and angiography data were obtained from the Danish Cause of Death Registry and the Western Denmark Heart Registry. Final diagnosis of AMI and the onset of BBB were determined by expert consensus. Patients were divided into 4 groups +/-AMI and +/- BBB. Mortality was evaluated by Kaplan-Meier plots using Log rank statistics.

Results
AMI was diagnosed in 954 patients, of whom 118 had BBBMI. In the 3951 patients without AMI, 436 had BBB. Coronary angiography (CAG) was performed in significantly fewer patients with BBBMI compared to patients with AMI without BBB (41% vs. 68%, p<0.001). In patients undergoing CAG, revascularization was more frequent in AMI patients without BBB (59% vs. 79%, p=0.002). BBBMI was categorized as new-onset in 43 patients. Significantly more patients with new-onset BBB underwent CAG compared to patients with established BBB (67% vs. 26%, p<0.001). Among those undergoing CAG, there was no difference frequency of revascularization between the groups (59% vs. 58%, p=0.99). Among patients with an adjudicated diagnosis of new-onset BBBMI 2/43=5% were triaged for acute angioplasty. Patients with BBBMI had the highest mortality of all groups (Log-rank p<0.001) (Figure).

Conclusions:
Patients with new-onset BBBMI seem to be difficult to diagnose based on ECG and symptoms, leading to low rates of invasive procedures despite high mortality. To improve outcome we recommend a more aggressive approach to diagnosing and triaging patients with BBB and chest pain.
Abstract 9963: The A2B Adenosine Receptor Antagonist (GS-6201) Improves Cardiac Remodeling and Dysfunction after Myocardial Infarction (MI) in Rat
Authors: Ling Haiyun , Chi Liguo , Zhong Hongyan , Zeng Aliya , Oliver Jason , Liles John , Zeng Dewan , Belardinelli Luiz , Dhalla Arvinder
Published: April 2024

Activation of A
2B
adenosine receptors in cardiac cells stimulates the release of inflammatory cytokines and fibrotic mediators. Adenosine concentration is elevated and A
2B
receptor expression is increased in hypoxic /ischemic myocardium. In the present study, the effect of GS-6201 (GS), a selective and potent A
2B
adenosine receptor antagonist (Ki 8.3 nM), alone or in combination with enalapril (ENL), was evaluated in a rat model of MI-induced cardiac remodeling and dysfunction (25-min myocardial ischemia followed by 5-wk reperfusion). Starting one week after MI, animals (n=8-13/group) were treated with GS (30 mg/kg), ENL (6 mg/kg), GS+ ENL or placebo
via
oral gavage once daily for 4 weeks. Serial echocardiographic assessments of LV geometry and function were conducted at baseline, 1, 3 and 5 weeks after MI. Significant cardiac dysfunction, hypertrophy and fibrosis developed in placebo treated animals. Compared to the placebo, GS, ENL and GS+ENL significantly improved LV ejection fraction (EF) and fractional shortening (FS), reduced LV end-systolic volume and decreased myocardial fibrosis at 5 week post MI. GS, ENL and GS+ ENL also significantly ameliorated plasma biomarkers including IL-6, TGF-β1 and BNP. Data were shown in Table 1. In summary, A
2B
adenosine receptor antagonist GS-6201 effectively reduced MI-induced LV remodeling and dysfunction in a rat model, possibly mediated through anti-inflammatory and anti-fibrotic mechanisms. The effects of GS-6201 and ENL were comparable, while the combination of GS-6201 with ENL provided an additional benefit.
Abstract 9968: Reduced Heart Rate Recovery after Exercise is Associated with Mortality After an ICD
Authors: Dougherty Cynthia M , Flo Gayle L , Goldman Todd L , Burr Robert L , Glenny Robb L
Published: April 2024

Background and purpose:
The period of recovery in heart rate (HRR) after exercise is thought to be mediated by parasympathetic reactivation. Abnormal heart rate recovery (<12 bpm during the 1st minute or < 25 bpm at 5 minutes) after exercise, has been shown to be a powerful predictor of mortality in those with coronary artery disease or heart failure (HF). HRR has not been studied in persons with an ICD. The purpose of this study was to examine the relationship between 1 and 5 minute HRR and 1 year mortality in patients undergoing exercise testing who have an ICD for either primary or secondary prevention of sudden cardiac arrest.

Methods:
149 patients who had a previous ICD implant (39% primary indication, 61% secondary indication, mean age 54+12.5 years, 76% male, 3.7+4.3 years since implant, 100% taking beta blockers) entered a clinical trial of exercise after an ICD. At baseline study entry, they completed a cardiopulmonary exercise test using a modified Balke treadmill protocol. HRR was calculated as the difference between peak exercise HR and 1 and 5 minutes into the recovery period using 12 lead EKG recordings. Analysis of variance was used to determine if HRR was significantly related to 1 year mortality after study entry.

Results:
There were 4 deaths within the 1st year after study entry (2.6%), all had a history of HF. Three deaths were due to HF and 1 was due to cancer. HRR was significantly reduced in those who died at both 1 minute (mean+SD; 7.5+6.2 bpm vs. 18.3+8.1 bpm, F=2.64,
p
=0.009) and at 5 minutes (19.2+6.0 bpm vs 38.7+13.9 bpm, F=2.76,
p
=0.006) when compared to those who did not. At baseline, there was statistically higher HRR in secondary prevention (19.4 bpm vs. 16.3 bpm at 1min (
p
=0.42) compared to primary prevention (40.7 bpm vs. 33.8 bpm at 5min (
p
=0.007). HRR was not related to ICD shocks.

Conclusions:
Those who have an ICD for primary prevention with a history of HF had lower HRR after exercise testing and higher 1 year mortality than those with a secondary prevention ICD. HRR is a useful marker of autonomic dysregulation and risk for mortality in those with HF who have an ICD.
Abstract 18: Differential Effect of Analyze Early versus Analyze Late prior to Initial Rhythm Analysis in Out-of-Hospital Cardiac Arrest: the Role of EMS Agency
Authors: Rea Thomas D , Prince David , Morrison Laurie , Callaway Clifton , Aufderheide Tom , Daya Mohamud , Stiell Ian , Christenson James , Powell Judy , Warden Craig , van Ottingham Lois , Kudenchuk Peter , Weisfeldt Myron
Published: April 2024

Background:
An effective resuscitation strategy in one community may not be effective in another community. We hypothesized that a strategy that prioritized initial Emergency Medical Services (EMS) rhythm analysis (Analyze Early) would provide a survival advantage among EMS systems with lower baseline ventricular fibrillation (VF) survival, while one prioritizing initial EMS CPR (Analyze Late) would provide a survival advantage among systems with higher baseline VF survival.

Methods:
We conducted an ancillary study of Analyze Early versus Analyze Late randomized trial of the Resuscitation Outcomes Consortium. Subjects were stratified according to pretrial EMS agency VF survival and their randomization arm. The primary outcome was survival to hospital discharge with favorable functional status. We used a binomial family mixed-effects model to determine whether outcomes from the trial intervention differed according to pretrial EMS agency VF survival.

Results:
Characteristics were similar among patients randomized to Analyze Early (n=4964) versus Analyze Late (n=4426). For EMS agencies with pretrial VF survival ≤20%, Analyze Early compared to Analyze Late was associated with a higher likelihood of favorable functional survival (5.5% versus 3.8%, OR=1.50 [1.11,2.0]). Conversely, among agencies with pretrial VF survival > 20%, Analyze Early compared to Analyze Late was associated with lower likelihood of favorable functional survival (6.1% versus 7.5%, OR=0.82 [0.66,1.02]). In the multivariable model, for every 10% improvement in pretrial VF survival, Analyze Late versus Analyze Early was associated with a 34% increase in the odds of favorable functional survival (OR=1.34 [1.07-1.66]).

Conclusion:
In this ancillary investigation of a clinical trial evaluating initial EMS CPR strategy, we observed a robust interaction indicating the Analyze Early strategy was associated with greater survival among EMS agencies with lower pretrial VF survival while the Analyze Late strategy was associated with greater survival among EMS agencies with a higher pretrial VF survival. The findings support distinct EMS CPR strategies based on a system’s baseline VF survival in order to achieve optimal outcomes following out-of-hospital cardiac arrest.
Abstract 18002: S-adenosylhomocysteine Levels May Better Differentiate Between Normal Control, Subjects With Ckd Stages 3 and 4, and Subjects on Hemodialysis
Authors: Bottiglieri Teodoro , Williams Matthew , Arning Erland , Filardo Giovanni , Fenves Andrew Z , East Cara
Published: April 2024

Patients on hemodialysis have higher levels of plasma total homocysteine (tHcy) and are at higher risk for atherosclerotic cardiovascular and vascular events, including death. However, secondary prevention trials to date have not shown any reduction in recurrent atherosclerotic events with B vitamin supplementation that lowers tHcy levels. Because high tHcy levels are still a good predictor of CV events, we investigated whether other metabolites related to tHcy metabolism and the methylation cycle may be altered in subjects at various stages of chronic kidney disease.

Methods:
We measured 6 intermediates of the methylation cycle in plasma using liquid chromatography mass spectroscopy: tHcy, S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), cystathionine, asymmetric dimethylarginine (ADMA), and symmetric dimethylargine (SDMA). Subjects included 92 subjects enrolled in longitudinal studies of healthy aging and dementia (Controls), 21 subjects with chronic kidney disease stages 3 and 4 (CKD), and 25 subjects on hemodialysis (Dialysis). All samples were collected between 2004 and 2012.

Results:
T-test analysis (corrected for multiplicity using Bonferoni correction) results show that all 6 metabolites were statistically significantly higher (p-values <0.05) in the CKD subjects than the Controls, and again statistically significantly higher (p-values <0.05) in Dialysis subjects than in CKD subjects (see Figure). While ADMA may be an independent risk factor for CAD, both tHcy and SAH levels were the most discriminatory: tHcy levels were 2.8 fold higher in CKD and 4 fold higher in Dialysis; SAH levels were 2.9 fold higher in CKD and 8.7 fold higher in Dialysis.

Conclusion:
SAH is a potent inhibitor of methylation reactions and has been implicated in causing vascular pathology. Elevated levels of SAH in plasma may provide greater discrimination in assessing risk of vascular disease in patients with chronic kidney disease.
Abstract 18025: Greater Consumer Nutrition Environment Disparities Are Associated With Lower Levels of Neighborhood Wellness
Authors: Culver Kristin N , Stephens Kelly D , Magzamen Sheryl , Shay Christina M
Published: April 2024

Introduction:
Poor AHA Healthy Diet Scores are a major obstacle to the improvement of cardiovascular (CV) health in the U.S. population. Food accessibility and availability have been widely recognized to influence eating behaviors that lead to obesity and adversely influence CV health status. The purpose of this investigation is to examine associations between the consumer nutrition environment and level of community wellness in a Southwestern metropolitan area of the United States (U.S.).

Methods:
The Nutrition Environment Measures Survey in Stores (NEMS-S) was used to assess the availability, quality, and price of healthy food options in supermarkets located in Oklahoma County, Oklahoma. NEMS-S is a validated measure that assesses a variety of food products commonly purchased in the U.S., including low-fat milk, fruits, vegetables, lean meats, processed foods, whole grain breads, lower-calorie/-fat food options, and sugar-sweetened beverages. The Oklahoma County Wellness Score was calculated for all regional ZIP codes according to major health and socioeconomic indicators. NEMS-S scores were compared between ZIP codes with highest (n=11) and lowest (n=11) quartiles of Wellness Score.

Results:
High Wellness score ZIP codes exhibited significantly higher overall NEMS-S scores compared to those with low Wellness Scores (38.0 vs. 30.6, p=0.003). Although NEMS-S food quality and price scores were similar across ZIP code Wellness Scores, food availability score was significantly higher in high Wellness Score ZIP codes compared to ZIP codes with low Wellness Score (27.9 vs. 2.6, p<0.001). ZIP codes with lower NEMS-S scores also had a higher percentage of households lacking access to a personal vehicle (6.1 vs. 16.0, p=0.001), higher proportion of minority population (50.9% vs. 20.7%, p=0.015), and lower median household income ($27,954 vs. $61,370, p<0.0001) compared to high NEMS-S Score ZIP codes.

Conclusions:
Consumer nutrition environment disparities that limit access to healthy food options are negatively associated with regional indicators of health and socioeconomic status. Promoting healthy food availability in neighborhoods with low health status may be a successful strategy for improving the CV health of the U.S. population.
Abstract 18068: Basis for a Major Genetic Alteration in Essential Hypertension: Inherited Defect in RBC-K Function and Oxygen Transport
Authors: Delgado-Almeida Antonio R , Delgado-Lelievre Maria C
Published: April 2024

For decades, the pathogenesis and management of hypertension have been focused on dietary salt consumption, low potassium (K) intake, or hormonal factors triggering elevation of BP.

In this context, our description of an inherited defect in RBC-K transport serially recorded in hypertensive subjects and in 52% of their normotensive adolescents offspring implies a genetic defect from erythropoietic cells and a biochemistry abnormalities in the circulating RBC as K-dependent pyruvate kinase activity for ATP synthesis, or allosteric K-O2 binding by hemoglobin, recently described by our Laboratory.

Methods:
A pedigree analysis was performed in randomized hypertensive patients (HT, aged ≥30-years) with essential hypertension (BP>140/90 mmHg), confirmed in the last 3-years, and having low RBC K content (<92 mmol/l of cell). Normotensive (NT) group were healthy subjects matched for sex-age-race and having normal BP and higher RBC-K. Family data includes sex-age-race of parents, siblings, spouses, children and presence of hypertension, diabetes (D), coronary heart diseases (CHD) and Stroke. For each family the number of deceased, age and cause of death were accurately obtained.

Results:
Fifty two hypertensive subjects disclosed family data (104 parents, 219 siblings, 24 spouses and 64 children= 411 cases) with large number of HT and CV disease: a) Parents: 63 hypertensive and 15 diabetic HT (75% incidence) with 3 AMI, 3 Stroke, 1 CRF and 21 CV deaths at age 58±7; b) Siblings: 142 out of 219 were HT (64.8 %; range 33-90%), 7 of them Stroke, 4 DM, CAD 15, 25 CV deaths at age 58±10 year; c) spouse 8 HT 33 %, children: <30 years (9, 14% HT), ≥30 years, 15 HT, 23%), the remaining being NT. From 104 HT parents were born 142 HT (17 CV deaths, 125 alive, aged 52±6).

In contrast, from 24 NT subjects there were: 48 parents, 153 siblings, 16 spouses and 48 children (total 265): a) Parents: 12 HT (25%), 2 AMI, 5 CAD, 3 DM, 13 no CV deaths at age 73±7 years; Siblings: 14 HT (9.2%) 7 DM, CV, no deaths, all alive aged 52±7; c) spouses HT 29%, children 7 HT, 14.5%. From 48 NT parents were born only 14 HT subjects.

In Conclusion:
This study strongly suggests the presence of a major hereditary defect in essential hypertension, involving defective RBC-K transport and function.
Abstract 18082: Differences in Ca2+ Cycling in Atrial Myocytes Isolated From Ventricular-Tachypaced Hearts vs. Atrial Tachypaced Hearts: Implication That Aberrant Ca2+ Cycling Contributes More AF Initiation Than to AF Maintenance
Authors: Aistrup Gary , Yoo Shin , Grubb Soren , Kay Richard , Monnier Chloe , Kunamalla Aaron , Wasserstrom J. Andrew , Arora Rishi
Published: April 2024

Background:
We have recently paid much attention to Ca2+ waves in canine and human atrial myocytes that occur only upon rapid pacing, which we have termed “triggered Ca2+ waves”. The temporal character of triggered Ca2+ waves suggests that they are likely to affect action potential duration beat-to-beat, and so could prompt dispersion of repolarization predisposing to reentrant arrhythmias. We therefore asked whether Ca2+ waves are prevalent in atrial myocytes isolated from failing hearts (proarrhythmic substrate) and/or hearts in atrial fibrillation (AF).

Methods:
Atrial myocytes were isolated from normal hearts (canine & human), failing hearts (4-6 weeks ventricular tachypaced; canine only) and hearts in atrial fibrillation (canine_5 weeks atrial tachypaced canine hearts; human_in AF), and examined (@ 37°C) for the incidences triggered Ca2+ waves and Ca2+ alternans during pacing at 1000-200ms cyclelengths (CLs) using Ca2+ fluorescent confocal microscopy.

Results:
Triggered Ca2+ waves were much more prevalent in atrial myocytes from normal and failing hearts than in atrial myocytes from heart in AF (incidence: 67% of normal canine, 59% of normal human, 75% of failing canine, 9% of canine AF, 14% of human AF). However, isoproterenol was effective in abolishing triggered Ca2+ waves in atrial myocytes from normal and AF hearts, but not in atrial myocytes from failing hearts. While there was less aberrant Ca2+ cycling in atrial myocytes from AF hearts, Ca2+ alternans were proportionally more prevalent in these myocytes compared to that in atrial myocytes from failing and normal hearts (incidence: 21% of normal canine, 34% normal human, 15% failing canine, 27% of canine AF, 76% human AF). Most recently we have found that reactive oxygen species inhibitors (mitoTEMPO, apocynin) significantly suppress (
↓
~80%, p<0.05) the incidence of triggered Ca2+ waves in atrial myocytes from failing heart.

Conclusions:
Our results suggest that abnormal Ca2+ cycling in the form of triggered Ca2+ waves, which may be manifest consequent to the oxidative stress that occurs upon heart failure, may play a more prominent role in the initiation of AF, while other mechanisms (i.e., alternans) contribute more after the establishment of AF and its maintenance.