bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18554: The Association of Diagnostic Criteria for Myocardial Infarction and Peri-Operative Cardiac Risk Factors in Vascular Surgery Patients
Authors: Cove Christina L , Hamburg Naomi , Eberhardt Robert , Rybin Denis , Kalish Jeffrey , Eslami Mohammad , Farber Alik , McPhee James
Published: April 2024

Background:
The inclusion of cardiac biomarkers and ST-T changes on electrocardiography in the diagnostic criteria for myocardial infarction (MI) has increased the apparent incidence of infarction in the general population. The impact of re-defining MI on the incidence and risk of peri-operative MI is unclear. We evaluate the association between diagnostic criteria changes and incidence of and risk factors for peri-operative MI in vascular surgery patients.

Methods:
Patients who underwent non-emergent vascular surgery between 2005 and 2011 were identified from the American College of Surgeons’ National Surgical Quality Improvement Program (NSQUIP) multi-center database. In 2005, MI was defined by new Q-waves on electrocardiography. In 2009, the definition included variable electrocardiographic evidence (ST elevation, new left bundle branch block, or new q-waves) or an elevation of cardiac troponin greater than 3 times the upper level of normal. Baseline characteristics were identified, and yearly incidence of MI was determined. Multivariable regression was used to determine risk factors associated with MI according to the old and new definitions.

Results:
Of 70,811 patients who underwent vascular surgery between 2005 and 2011, 40,017 (57%) were ≥ 70 years old, and 46,206 (65%) were male. High-risk vascular surgery (open abdominal aortic aneurysm repair or aorto-bifemoral bypass) was performed in 7,359 (10%) patients. Peri-operative MI more than tripled from the 2005-2008 to 2009-2011 time periods (1.5% vs. 0.4%; p<0.001). In multivariable analyses, significant risk factors for MI also changed from the earlier to later model (See Table).

Conclusions:
Re-defining MI increased the apparent incidence of and number of independent risk factors for peri-operative MI. The diagnostic criteria for MI utilized in prior cardiac risk prediction models should be considered when determining risk in patients undergoing non-emergent vascular surgery.
Abstract 18559: Inhibition of Mitochondrial Fission as a Novel Molecular Target to Attenuate Myocardial Ischemia-Reperfusion Injury: Critical Importance of the Timing of Treatment
Authors: Dong Yi , Undyala Vishnu V , Przyklenk Karin
Published: April 2024

Background:
Mitochondrial fragmentation (i.e., fission) has been implicated as: (i) a critical determinant of myocyte viability and, thus (ii) a potential molecular target for novel cardioprotective therapies. This concept is based on evidence that inhibition of fission, achieved by pharmacologic or genetic manipulation of DRP1 (dynamin-related protein 1: the key molecular regulator of fission) attenuates lethal myocardial ischemia-reperfusion injury. However, all studies have implemented treatment/genetic silencing as a pre-treatment; the effect of inhibition of fission, initiated in a therapeutically relevant manner (at reoxygenation) has, to date, not been explored.

Methods:
To address this issue, cultured HL-1 cells underwent 2 hrs of hypoxia + reoxygenation (R). Cells were given: (i) mdivi-1 (specific DRP1 inhibitor; 50 μM) 1 hr before hypoxia (pre-treat); (ii) mdivi-1 (50 μM) at reoxygenation (post-treatment); or (iii) vehicle. Time-matched normoxic cells served as controls. Endpoints included: (i) translocation of DRP1 to mitochondria, assessed at 2 hrs post-R; (ii) expression of cleaved caspase 3 (harbinger of apoptosis), assessed at 2 hrs post-R; and (iii) cell viability quantified by trypan blue staining at 20 hrs post-R.

Results:
As expected, pre-treatment with mdivi-1 inhibited translocation of DRP1 to the mitochondria (not shown), attenuated the cleavage of caspase 3 (right: p<0.05), and preserved cell viability (left: p<0.05 vs vehicle). Post-treatment with mdivi-1 had a similar, favorable effect on caspase 3 cleavage (right: p<0.05), but, in contrast, exacerbated cell death (left: p<0.0001 vs vehicle).

Conclusion:
We report novel evidence that mdivi-1, given at reoxygenation, has a paradoxical and dissociative effect on apoptotic vs necrotic cell death. Moreover, these data provide initial insight into an apparently complex temporal relationship between inhibition of mitochondrial fission and cardioprotection.
Abstract 18560: Defective Ca
2
+ Homeostasis Contributes to Arrhythmia in Transgenic Rabbit Model of LQT2 Syndrome
Authors: Terentyev Dmitry , Cooper Leroy , Li Weiyan , Lu Yichun , Terentyeva Radmila , Peng Xuwen , Koren Gideon
Published: April 2024

Introduction:
Loss-of function mutations in HERG potassium channels in Long QT2 syndrome are associated with sudden cardiac death triggered by sympathetic surge. In various models of cardiac disease changes in calcium (Ca) homeostasis, associated with upregulated plasmalemmal Na/Ca exchanger (NCX) and/or hyperactive ryanodine receptors (RyRs), have been linked to increased risk of arrhythmia.

Methods and Results:
The aims of this study were to investigate possible changes in Ca homeostasis in cardiomyocytes derived from from the hearts of LQT2 rabbits and to determine whether similar changes contribute to the triggering of early afterdepolarizations (EADs) characteristic of LQT2 myocytes under β-adrenergic stimulation. Parameters of Ca handling were measured in ventricular myocytes enzymatically isolated from LQT2 and littermate control hearts using confocal Ca imaging and whole cell patch clamp. Ca imaging revealed no changes in amplitude of Ca transients in intact myocytes and sarcoplasmic reticulum (SR) Ca content assessed by measuring amplitude of transients evoked by rapid application of caffeine. A two-fold increase in rate of decay of caffeine-induced Ca transients in LQT2 myocytes vs. controls indicated increased NCX activity. Experiments in saponin-permeabilized cells using a SR-entrapped low-affinity Ca indicator revealed ~2-fold increase in RyR-mediated SR Ca leak in LQT2 myocytes in comparison with controls. In contrast to controls, current-clamped LQT2 myocytes exposed to β-adrenergic agonist isoproterenol exhibited prolonged plateau of action potentials (AP) at -10 - 0 mV accompanied by aberrant Ca releases and phase 3 EADs. Importantly, complete exhaustion of SR [Ca] by incubation of LQT2 cells with SERCA inhibitor thapsigargin or 10 mM caffeine, shortened APD and completely abolished EADs.

Conclusion:
Functional changes in RyR and NCX underlie preserved systolic Ca transients in LQT2 myocytes under basal conditions and may contribute to stress-induced arrhythmia by maintaining the plateau of AP at voltages ideal for reactivation of plasmalemmal Ca channels and generation of EADs.
Abstract 18568: Normal Angiographic Appearance of the Coronary Arteries is Common in Antiphosopholipid Syndrome Patients Presenting With Acute Coronary Syndrome
Authors: Mejia Lopez Eliany , Yedlapati Neeraja , Spevack Daniel M
Published: April 2024

Background:
Antiphospholipid syndrome (APLS) is known to be associated with Acute Coronary Syndrome (ACS) due to coronary artery thrombosis or embolism. Because individual cases of ACS with normal angiographic appearance of the coronary arteries have been reported in this population, we aimed to determine the prevalence of this presentation amongst patients with known APLS at our institution.

Methods:
Our institutional database was queried for all patients testing positive for antiphospholipid antibodies (n=575) between 2000 and 2012. From this sample, we identified 46 patients having cardiac catheterization. ACS (n=32) was defined as the presence of angina chest pain, ECG with ST segment or T-wave abnormalities and troponin-I > 0.1 mg/dL.

Results:
Normal appearing coronary arteries, without evidence of atherosclerosis or embolism, were found in 8 patients (52±7 years, 5 female) with APLS (lupus anticoagulant n=5; anti-cardiolipin n=5; anti-B2-GP1 n=3) presenting with ACS. All 8 patients had history of prior arterial (stroke n=5) or venous thrombosis (n=3). Median troponin-I was 0.30 mg/dL [range 0.15, 0.50]. One subject was found to have diffuse coronary artery spasm, which reversed following administration of intra-coronary nitroglycerine. One patient had a regional wall motion abnormality in a single territory and another patient had global ventricular dysfunction. Median left ventricular ejection fraction was 60% [range 30, 60].

Conclusions:
A high proportion of patients with APLS presenting with ACS did not have evidence of either coronary thrombosis or embolism on angiography. This clinical presentation is suspicious for either coronary artery spasm or myopericarditis.
Abstract 18576: Areas of Disease Knowledge as Differential Predictors of Outcomes Among Adolescents and Adults With Congenital Heart Disease
Authors: Jackson Jamie L , Misiti Brian , Daniels Curt J , Vannatta Kathryn
Published: April 2024

Introduction:
Adolescent and adult survivors of congenital heart disease (CHD) often have difficulty reporting diagnosis and surgical history, as well as reasons for follow-up care and disease heritability. However, aspects of disease knowledge associated with patients’ self-care or their health-related quality of life (HRQoL) are not well understood. The current study aimed to assess multiple dimensions of disease knowledge and their relationships with patient self-management and HRQoL among survivors of CHD.

Methods:
Individuals with CHD (N = 185) were recruited from adult and pediatric cardiology clinics (93% recruitment rate). Participants were 15 to 39 years of age (M = 24.7 + 6.9) with simple (22%), moderate (44%), or complex (34%) lesions. Participants were asked to recall their diagnosis, surgical history, and current medications (RECALL), identify complications of CHD for which they are at risk and symptoms of those complications (RISK), and answer general questions about CHD, (e.g., duration of care, endocarditis, and heritability) (GENERAL). Disease knowledge was reported in percent accuracy. Measures of self-management included self-reported saturated fat intake (DIET) and frequency x intensity of physical activity (ACTIVITY). HRQoL was measured by the Physical (PCS) and Mental (MCS) Component Scales of the SF-36. Hierarchical regression analyses were conducted with age, lesion severity, RECALL, RISK, and GENERAL knowledge as predictors of self-management and HRQoL.

Results:
RISK and GENERAL knowledge were the only significant predictors of DIET (β = -0.19, p = 0.038, β = -0.22, p = 0.009) and ACTIVITY (β = 0.20, p = 0.043, β = -0.21, p = 0.017). However, age (β = -0.18, p = 0.037) and RECALL knowledge (β = 0.18, p = 0.022) were the only significant predictors of PCS. None of the variables significantly predicted MCS.

Conclusion:
This is the first study to report an association between disease knowledge and self-management among survivors of CHD. The findings suggest that understanding one’s future risks and general self-care may be more predictive of health behaviors than knowing personal medical history. Therefore, different aspects of disease knowledge may need targeting for intervention depending on the type of patient outcome.
Abstract 18592: A Hmg-Coa Reductase Inhibitor (Statin) Directly Activates Endothelial Erk5 and Prevents Endothelial Dysfunction and Acute Cardiac Allograft Rejection
Authors: Le Nhat-Tu , Takei Yuichiro , Izawa-Ishizawa Yuki , Heo Kyung-Sun , Lee Hakjoo , McClain Carolyn , Cushman Hannah , Smrcka Alan V. , Miller Benjamin , Ko Kyung Ae , Morrell Craig , Fujiwara Keigi , Akaike Masashi , Abe Jun-ichi
Published: April 2024

Background:
Statins inhibit HMG-CoA reductase and are principal therapeutic agents for the treatment of hypercholesteremia. However, statins also have cholesterol-independent effects such as improving endothelial cell (EC) functions, preventing cardiovascular diseases and suppressing cardiac allograft rejection. How statins exert these cholesterol-independent effects is not known. Because ERK5 exerts beneficial effects on ECs and is anti-atherogenic, it may play a role in these statin effects.

Methods and Results:
We screened small molecules that activate ERK5 using high throughput screening and found that several statins were strong activators of ERK5 transcriptional activity. We found pitavastatin was especially effective. It increased ERK5 transcriptional activity and the promoter activity and mRNA expression of KLF2 and eNOS in ECs. These effects were abolished by the depletion of ERK5 but not its direct upstream kinase, MEK5. We found that pitavastatin dose-dependently activated ERK5 kinase activity in an in vitro kinase assay, suggesting that ERK5 is a direct target of statins. To examine roles of statin in EC ERK5 activation in vivo, we used inducible endothelial ERK5 knock out (EC-ERK5-KO) mice. When EC ERK5 was depleted, these mice exhibited significantly increased EC inflammation (increased leukocyte rolling) and dysfunction (impaired vascular reactivity), and these conditions could not be corrected by pitavastatin. However, when the EC inflammation and dysfunction were induced in wild type (WT) mice by STZ treatment (i.e. diabetic), their conditions were reversed by pitavastatin. Interestingly, the heart from EC-ERK5-EKO mice had significantly increased mRNA levels of inflammatory genes (TNFα, MCP1, IL-1, IL-6) and decreased expression of an anti-inflammatory cytokine, IL-10. Hearts from EC-ERK5-KO and littermate WT mice were used to perform prolonged allograft survival in a full allomismatch combination model. After 5 days of transplantation, a robust increase in inflammatory gene expression was inhibited by pitavastatin in WT but not in EC-ERK5-EKO hearts.

Conclusion:
These data suggest a crucial role of endothelial ERK5 in the pleiotropic effects of statins on EC dysfunction and allograft rejection.
Abstract 186: NHE-1 Inhibition Reduces Rigor and Hypercontracture in Isolated Cardiomyocytes During Ischemia and Reperfusion
Authors: Velmurugan Sathya , Radhakrishnan Jeejabai , Baetiong Alvin , Gazmuri Raúl J
Published: April 2024

Background:
During ischemia, anaerobic metabolism prompts intracellular acidosis with activation of the sodium hydrogen exchanger isoform-1 (NHE-1), resulting in intracellular Na+ overload consequent to reductions in Na+-K- ATPase activity. The Na+ excess prompts Ca2+ entry through the sodium-calcium exchanger, leading to Ca+ overload. Ca+ overload, predisposes cells to hypercontracture upon reoxygenation. NHE-1 inhibition reduces Na+ overload and the subsequent Ca+ overload. We developed a programmable system to model ischemia and reperfusion by dynamically blending O2, CO2, and N2 and used it to model changes in gas tension at the tissue levels during ischemia and reperfusion. We validated the model by comparing the effects of reoxygenation with and without the NHE-1 inhibitor zoniporide in isolated adult rat cardiomyocytes.

Methods:
The set-up included: (i) a programmable dynamic gas blender developed by us, (ii) equilibration of ischemic buffer with anoxic gas mixture at 3-5 LPM and perfusion within an imaging chamber at 2.5 ml/min, (iii) a glass reservoir and stainless steel tubing to avoid gas diffusion, (iv) an acrylic hood, constantly flushed with anoxic gas mixture, covering the chamber on the stage of the microscope, and (v) an O2 microelectrode to continuously monitor PO2 in the chamber. The set-up resulted in PO2 of 0 mmHg during ischemia. The cells were subjected to 15 min of baseline stabilization, 45 min of ischemia, and 120 min of reperfusion. Zoniporide (at a final concentration of 3 μM) was administered starting at 10 min of ischemia and was maintained throughout reperfusion.

Results:
Zoniporide significantly attenuated development of rigor and subsequent hypercontracture (P=0.001, Gehan Breslow survival analysis).

Conclusion:
The newly develop system reproduced at the cell level effects of ischemia and reperfusion. These effects were attenuated by NHE-1 inhibition as it has been reported in isolated organs and in the in situ heart.
Abstract 18604: The Prognostic Value of Diuretic Dose in Stable Chronic Heart Failure Patients
Authors: Triggiani Marco , Manerba Alessandra , Lupi Laura , Suardi Silvia , Pizzuto Annalisa , Dasseni Nicolò , Mbadjeu Houndjeu Arnaud Romeo , Cesana Bruno Mario , Gheorghiade Mihai , Nodari Savina
Published: April 2024

Background:
High daily diuretic dose (DDD) in chronic heart failure (HF) patients (pts) is related to cardiac and renal dysfunction but its relationship with outcomes in this population is still not completely understood. The aim of this study was to evaluate the prognostic implications of DDD in pts with chronic HF.

Methods:
Retrospective analysis of pts with HF and reduced Left Ventricular Ejection Fraction (LVEF<45%), followed at our outpatient HF clinic. Inclusion criteria were optimized therapy and clinical stability (neither events nor therapeutic changes) in the previous 3 months. Hypervolemic or euvolemic status was defined according to the sodium retention score (NaRS). We considered DDD as a continuous variable. Patients were followed prospectively for the occurrence of the composite endpoint cardiovascular (CV) death and hospitalizations for HF or CV causes after one- year follow-up.

Results:
A total of 528 pts (mean age 66.9 ± 13 years, 82% male) were enrolled. Overall, at one-year follow-up, the composite endpoint occurred in 151 pts (28.6%). In table 1 are summarized clinical, laboratory and echocardiographic characteristics that at Univariate analysis were significantly correlated with the occurrence of the composite endpoint. In multivariable model, only LVEF (OR 0.97; CI 0.94-0.99; p = 0.029), DDD (OR 1.002; CI 1.0005-1.004; p = 0.011) and NaRS (OR 2.58; CI 1.52-4.39; p <0.001), were independently associated with events.

Conclusion:
In chronic stable HF patients, DDD appears to have an independent prognostic value. Additional analyses are needed to determine if high DDD may have the same independent predictive value after adjustment for the clinical congestion status of pts.
Abstract 18606: The Value of Cardiac Magnetic Resonance Imaging in Detection of Sub-Clinical Cellular Rejection
Authors: Barten Markus J , Garbade Jens , Bittner Hartmuth B , Mohr Friedrich W , Gutberlet Matthias M
Published: April 2024

Background:
Sub-clinical acute cellular rejection (ACR) after heart transplantation (HTx) is a major cause of cardiac allograft vasculopathy. But with endomyocardial biopsy (EMB) the detection of sub-clinical ACR is limited by sampling error, interobserver variability or the wide variability of frequency and duration to use this invasive interventional tool. Thus, we used cardiac magnetic resonance imaging (CMRI) to identify sub-clinical ACR after HTx.

Methods:
In total 73 patients with a mean age of 53±12 years were scanned 167 times with a 1.5T-MRI scanner using a standard myocarditis protocol to detect sub-clinical ACR. Myocardial edema and myocyte damage were determined by using specific “cut-off” values to determine inflammatory parameters of early- and delayed- enhancement as well as to determine water content. CMRI-results were correlated with results of EMB performed on the same day using the original ISHLT EMB guidelines to more accurately determine sub-clinical ACR.

Results:
In 87 (52%) out of 167 biopsies a rejection grade of 1A was diagnosed, whereas 16 biopsies (10%) were graded 1B, 2 biopsies (1.1%) 2A and 1 biopsy (0.5%) 3A, respectively. No rejection was diagnosed in 61 biopsies (36%).

Sensitivity, specificity and negative predictive value for rejection grade ≥1B were for (1) early-enhancement 64%, 70% and 93%; (2) delayed-enhancement 43%, 38% and 82%; (3) water content: 60%, 79% and 93%. In combination of all 3 parameters sensitivity, specificity and negative predictive value were: 71%, 66% and 94%.

Conclusion:
We showed that a combination of specific CMRI parameters have a high negative predictive value in early detection of sub-clinical ACR. Future clinical studies need further to evaluate CMR as an evolving tool in ACR.
Abstract 18609: MicroRNA-539 Upregulation Suppresses O-GlcNAcase in the Failing Heart
Authors: Muthusamy Senthilkumar , Watson Lewis J , Hong Kyung U , Jones Steven P
Published: April 2024

Background:
Cardiac metabolism and related signaling pathways are significantly altered in the failing heart. One such signal, O-linked β-N-acetylglucosamine (O-GlcNAc), represents an essential post-translational modification that modulates the function of many nuclear and cytoplasmic proteins, and, does so in a variety of diseases. O-GlcNAc modification is controlled by two antagonistic enzymes: O-GlcNAc transferase (OGT; adds O-GlcNAc) and O-GlcNAcase (OGA; removes O-GlcNAc). We recently reported reduced OGA expression in the failing heart, which is consistent with the pro-adaptive role of increased O-GlcNAcylation during heart failure; however, mechanisms of OGA regulation during heart failure remain unknown.

Methods and Results:
Using miRNA microarray analysis, we observed changes of several miRNAs at 5 d and 28 d post-myocardial infarction in mice (n=4/group) and, specifically, that miR-539 is significantly (p<0.05) elevated. Subsequent qRT-PCR analysis confirmed significant (p<0.05) upregulation of miR-539 at both time points (4.8 fold at 5 d and 2.9 fold at 28 d) in infarcted hearts compared to sham hearts. TargetScan predicted OGA as a potential target of miR-539. Indeed, co-transfection of OGA-3’UTR containing reporter plasmid and miR-539 overexpression plasmid significantly reduced the reporter activity compared to control in transiently transfected HEK 293 cells. To establish whether miR-539 suppresses OGA expression in cardiomyocytes, lentivirus based miR-539 overexpression system was used to transduce neonatal rat cardiomyocytes. Western blot analysis showed significant (~50%; p<0.05) reduction of OGA protein expression.

Conclusion:
These results demonstrate that miR-539 is upregulated during heart failure, binds to OGA-3’UTR, and can significantly suppress OGA expression in cardiomyocytes. This work identifies the first target of miR-539 in the heart and the first miRNA that regulates OGA. Manipulation of miR-539 may represent a novel potential therapeutic target in the treatment of heart failure and other metabolic diseases.
Abstract 18613: Utilization of High-Potency Statin Therapy Following Hospitalization for CHD Among Medicare Beneficiaries
Authors: Rosenson Robert S , Kent Shia , Brown Todd , Farkouh Michael , Levitan Emily , Yun Huifeng , Sharma Pradeep , Safford Monika , Kilgore Meredith , Muntner Paul , Bittner Vera
Published: April 2024

Background:
Evidence-based guidelines recommend high-potency statins for secondary prevention in high-risk patients including individuals hospitalized for coronary heart disease (CHD) events. In these patients, initiation of this therapy is recommended upon hospital discharge.

Aim:
Investigate the proportion of Medicare beneficiaries who fill a prescription for a high potency statin following discharge and within 365 days after hospital discharge for an incident CHD event.

Methods:
This study included Medicare beneficiaries ≥ 65 years with no documented CHD history in the prior year who were hospitalized and filled a statin following an incident CHD event (myocardial infarction or coronary revascularization procedure) in 2007, 2008 or 2009. High-potency statins included atorvastatin 20 mg to 80 mg, rosuvastatin 10 mg to 40 mg and simvastatin 40 to 80 mg daily.

Results:
Among 9,455 Medicare beneficiaries filling a statin following an incident CHD hospitalization, 33.8% and 40.2% filled prescriptions for high-potency statins within 90 and 365 days, respectively. The proportion filling a prescription for a high-potency statin declined between 2007 and 2009. After multivariable adjustment, more recent calendar time, progressively older age and higher Charlson scores were associated with a lower likelihood of filling a prescription for a high potency statins and Asians were more likely to fill a prescription for a high potency statin (Table).

Conclusions:
The majority of Medicare beneficiaries who will a statin following hospitalization for CHD do not fill a high potency statin. The under-utilization of high-potency statin therapy represents a major obstacle to lowering the burden of recurrent cardiovascular events.
Abstract 18615: Magnesium Sulfate Revisited: Administration of Magnesium Sulfate in the Early Post-Resuscitation Phase is Associated With Improved Survival and Neurological Outcomes in This Era of Therapeutic Hypothermia
Authors: Chang Wei-Tien , Huang Chien-Hua , Yuan Ang , Tsai Min-Shan , Hsu Chiung-Yuan , Wang Chih-Hung , Lin Shih-Chia , Lin Wen-Shia , Kao Hsiu-O , Ma Matthew Huei-Ming , Chen Shyr-Chyr , Chen Wen-Jone
Published: April 2024

Background:
Therapeutic hypothermia (TH) is associated with QT prolongation which may increase the risk of cardiac arrhythmia. Magnesium sulfate (MgSO
4
) has long been the standard treatment for long QT syndrome. In addition, magnesium has been shown to dilate cerebral blood vessels and improve the compromised brain perfusion in the post-resuscitation phase. It may also have a role in neuroprotection in hypoxic-ischemic encephalopathy. We therefore evaluated in a retrospective series the role of MgSO
4
in early post-resuscitation care in this era of TH.

Methods:
From Jan 2008 to May 2013, post-resuscitated patients who remained comatose when admitted to National Taiwan University Hospital were included. Univariate analysis was first employed for sorting out clinical factors associated with survival and neurological outcomes. Those reaching statistical significance were then entered in binary logistic regression analysis for searching independent predictors.

Results:
During this period, 231 patients were included. The mean age was 68.5 ± 16.4 years old and 141 were male. Thirty seven (16.0%) had initial rhythm of Vf/VT. The total CPR time was 21.9 ± 15.9 min. The patients receiving TH (n = 110) had significantly better survival (58.2% vs. 21.5%,
P
< 0.001) and neurological prognoses (20.9% vs. 6.6%,
P
= 0.001). MgSO
4
was administered in the early post-resuscitation phase in 74 patients (52 with TH, 22 without), and was associated with better survival (60.8% vs. 28.7%,
P
< 0.001) and neurological outcomes (21.6% vs. 9.6%,
P
< 0.05). In univariate analysis, TH, MgSO
4
, age, Vf/VT, shorter CPR time, lower epinephrine dose and no use of vasopressors in the post-resuscitation phase were associated with better survival and neurological outcomes, while seizure was associated with poorer neurological recovery. In binary logistic regression analysis, TH, MgSO
4
, Vf/VT and CPR time were independently associated with survival, while age, Vf/VT and seizure serve as independent predictors for neurological prognosis.

Conclusions:
Administration of MgSO
4
in the early post-resuscitation phase is associated with improved survival and neurological outcomes in this era of TH. Further well-designed prospective study is warranted for verifying its roles and potentials.
Abstract 18647: Gender Differences in the Relationship Between Depressive Symptoms and Coronary Events in Acute Coronary Syndrome Patients
Authors: Sanner Jennifer E , Morrison Alanna , Frazier Lorraine
Published: April 2024

Background:
Despite a decrease in acute mortality, a considerable number of patients who have acute coronary syndrome (ACS) go on to experience major adverse coronary events (MACE). The objectives of this prospective ACS study are to examine relationships between depressive symptoms and risk of subsequent MACE and most importantly, examine if gender differences exist. We hypothesized that the presence of depressive symptoms will be related to increased risk of MACE and gender differences will exist.

METHODS:
We analyzed 1194 patients enrolled during hospitalization for ACS. Patients were screened using the Beck Depression Inventory-II. Annual telephone interviews were conducted to obtain MACE data. MACE was defined and death, stroke, AMI, re-admission for ACS requiring vascularization. Basic descriptive statistics were determined and analysis of risk for MACE was conducted with logistic regression. Logistic regression models for occurrence of MACE included gender and depression as the independent variables. An interaction term for gender-by=depression was included in the model to test if the association of depression and MACE varies by gender.

RESULTS:
Of the 1104 with MACE data, 16% reported MACE. Of those, 33% were women and 67% were men. Women were older (64.19 ± 13) than men (61.06 ± 11.60) (p<0.0001) and were more likely to report a diagnosis history of diabetes (p=0.009), hypertension (p<0.0001), and stroke (p=0.005) than men. Men were more likely to report current smoking (p<0.0001) and alcohol (p<0.0001) statuses than women and were more likely to report a history of coronary angioplasty (p=0.001). Depressive symptoms were significantly related to MACE with a two-fold greater odds of subsequent MACE (OR 2.56, CI 1.80-3.63, p=<0.0001). Both men (OR 2.82, CI 1.85-4.28, p<0.0001) and women (OR 2.09, CI 1.12-3.91, p=0.020) experience greater odds of MACE when depressed. The association between depression and MACE did not vary significantly by gender (p=0.394).

CONCLUSIONS:
To conclude important gender differences were noted, but the association between depression and MACE did not vary significantly by gender. This study has the potential to add to the growing body of literature that suggests that gender-related differences exist with regard to ACS.
Abstract 18648: Heart Healthy Living: A Community-Based, Tailored Educational Program to Improve the Cardiovascular Knowledge and Health of African American Women
Authors: Sauris Aileen , Timmons Patricia , Rodriguez Fatima , Wang Yun , Foody JoAnne M
Published: April 2024

Background:
Low health literacy is a potential contributor to poor cardiovascular outcomes. Health literacy is lowest among the elderly, racial/ethnic minorities, those with low education level, the uninsured, and the publicly insured.

African American (AA) women suffer from a disproportionate burden of CV risk factors (RF) and low health literacy. We developed a community-based, tailored health education, nutrition, and exercise program, Heart Healthy Living (HHL) to address the unique challenges in AA women.

Methods:
HHL consisted of a 6-week program to improve the CV health literacy of AA women aged 18 years or older with at least one CV risk factor. The program consisted of weekly tailored CV health education and exercise classes. In weeks 1 and 6, participants completed a validated Heart Disease Knowledge Questionnaire, blood pressure and weight were checked.

Results:
Participants included 32 AA women with an average age of48 years. Participants had high rates of hypertension (55%) and obesity (68%). Participants experienced an age-adjusted weekly weight loss of 0.5 lbs and an age-adjusted total weight loss of 2.7 lbs (p<0.001). There was a 40% relative decline in rates of HTN after completion of the program. At baseline, participants scored <50% on the validated Heart Disease Knowledge Questionnaire; however after completion of the program this improved significantly (Figure).

Conclusion:
We found that a tailored health education and exercise program resulted in improved CV health literacy in AA Women. Our data suggests an intensive CV education and exercise program, improved health literacy disparities and CV RF in AA women. Larger and longer studies of HHL are ongoing to determine whether these results are replicable and sustainable.
Abstract 18692: Survival From Sudden Cardiac Arrest in Women Compared to Men
Authors: Marijon Eloi , Teodorescu Carmen , Dumas Florence , Reinier Kyndaron , Mustafic Hazrije , Evanado Audrey , Narayanan Kumar , Bougouin Wulfran , Lamhaut Lionel , Jost Daniel , Pochmalicki Gilbert , Huertas Vazquez Adriana , Stecker Eric , Jerger Katherine , Chugh Harpriya , Gunson Karen , Jui Jonathan , Celermajer David S , Jouven Xavier , Chugh Sumeet
Published: April 2024

Introduction:
There is controversy regarding comparative survival from sudden cardiac arrest (SCA) between the sexes that needs further investigation.

Hypothesis:
Women present with a better outcome after resuscitation for SCA, compared to men.

Methods:
Female and male SCA cases aged 15-75 years were pooled and compared from 2 large community-based SCA programs across the Atlantic, a Northwestern US metro region and the Greater Paris, France metro area. We compared incidence, characteristics, and outcome (return of spontaneous circulation, ROSC).

Results:
Of the 7,357 SCA cases, 1783 (24.8%) were female, an incidence of 22.8 (95% CI 22.6-23.0) per 100,000 per year. Compared to men, the overall relative risk of SCA in women was 0.46 (95% CI 0.40-0.54) in US and 0.32 (95% CI 0.31-0.33) in France. Women were older (mean age 57.5±13 vs. 56.3±12, P<0.001), with higher rates of diabetes (40.4 vs. 35.6%, P=0.02) and hypertension (59.0 vs. 53.0%, P=0.006), lower proportion witnessed (63.9 vs. 70.0%, P<0.001), with less bystander cardiopulmonary resuscitation (29.0 vs. 32.3%, P<0.01), and lower proportion of ventricular fibrillation (28.7 vs. 42.4%, P<0.001). Response times were not statistically different in women compared to men (P=0.25). Proportion of ROSC was similar in both sexes (27.82 vs. 27.85%, P=0.98). After adjustment for confounding factors, women were associated with better outcome (OR 1.54, 95% CI 1.30-1.82, P<0.001): 1.35 (95% CI 1.10-1.69, P=0.006) in US, and 1.72 (95% CI 1.28-2.32, P<0.001) in France.

Conclusions:
SCD in women has distinct characteristics and outcome compared to SCD in men. Our results suggest higher propensity for survival in women compared to men that warrants further investigation.
Abstract 18709: Older Former Smokers with <32 Pack-Years of Prior Smoking and <15 Years of Abstinence Have Lower Risk of Incident Heart Failure and Cardiovascular Mortality But Not of All-Cause Mortality: Findings From a Prospective Population Study
Authors: Ahmed Amiya A , Morgan Charity J , Fonarow Gregg C , Prabhu Sumanth , Bittner Vera , Patel Kanan , Deedwania Prakash , Filippatos Gerasimos , Anker Stefan D , Allman Richard M , Aronow Wilbert , Ahmed Ali
Published: April 2024

Background:
According to the US Surgeon General, the cardiovascular (CV) risk of former-smokers may become similar to that of never-smokers after 15 years of abstinence. We have previously demonstrated that former heavy smokers (≥32 pack-years) may still be at increased risk of incident heart failure (HF) despite >15 years of abstinence (Circulation 2010; 122:
A17788
and Circulation 2011; 124:
A18263
). In the current study, we examined the risk of incident HF and mortality in former light and heavy smokers who quit ≤15 years ago.

Methods:
Of the 3410 community-dwelling adults, age ≥65 yrs, free of baseline HF, in the Cardiovascular Health Study, 2557 were never-smokers and 853 were former-smokers who quit ≤15 (median, 8) years ago. Heavy smoking was defined as ≥32 PY of smoking. Cox regression models were adjusted for age, sex and race only as other baseline confounders were likely affected by prior smoking and acted as mediators.

Results:
Unadjusted and age-sex-race adjusted associations of former smoking with outcomes during 13 years of follow-up are displayed in the
Table
.

Conclusions:
We found no evidence of higher risk for incident HF and CV mortality among former light smokers who quit 15 or fewer (median, 8) years ago when compared with never smokers, although the risk for all-cause and non-CV mortality was higher. Former heavy smokers had significantly higher risk for all outcomes.
Abstract 18718: Differential Effects of Nebivolol and Metoprolol on Oxidative Stress Markers and Circulating Progenitor Cells
Authors: Poole Joseph , Neuman Robert , Kavtaradze Nino , Morris Alanna , Binongo Jose , Khan Ali , Sher Salman , Quyyumi Arshed
Published: April 2024

Background:
Unlike traditional beta-blockers, nebivolol activates nitric oxide (NO) release via partial agonist activity at beta-2/3 receptors. We hypothesized that this property of nebivolol compared to metoprolol would improve oxidative stress (OS) and mobilize progenitor cells (PCs) that are known to be enhanced by NO, and ultimately contribute to improved vascular health.

Methods:
Thirty-two hypertensive subjects (age 54±10 years, 57% male, 83% African American) were randomized in a double-blind, cross-over study to receive either nebivolol or metoprolol for 3 months each. Of the 32 subjects randomized, 30 subjects successfully completed the trial. Two subjects did not complete the study due to serious adverse events. Nebivolol was titrated from 5mg to 20mg daily (mean 12mg) and metoprolol XL from 50mg to 200mg daily (mean 123mg). All other hypertensive therapy was kept constant. Measurements were made at baseline and on each drug after 3 and 6 months. OS was estimated from plasma levels of glutathione that reflects increased oxidative stress at lower levels. Circulating PCs were measured using flow cytometry for CD34+ and CD34+/CD133+ positive cells in mononuclear cell pools (CD45med). Arterial stiffness was measured as pulse wave velocity and augmentation index using the Sphygmacor device.

Results:
Compared to baseline, both nebivolol and metoprolol significantly and equally lowered systolic and diastolic BP (p<0.01). Nebivolol, but not metoprolol significantly increased the glutathione level (from 1.08 to 1.50μM; p=0.04). Both nebivolol and metoprolol significantly increased circulating numbers of CD34+/CD133+ PCs compared to baseline by 28% and 18%, respectively (p=0.02, for both). Neither nebivolol nor metoprolol significantly changed indices of arterial stiffness.

Conclusion:
Beta adrenergic antagonists increase circulating levels of PCs indicating improved regenerative capacity. Nebivolol, but not metoprolol, reduces oxidative stress, measured as plasma glutathione. The lack of translation of these effects on arterial stiffness may be secondary to the short duration of therapy in a treated population.
Abstract 18728: Patterns of Antiplatelet Use in Patients With Stable Atherosclerosis: Insights From the Tra 2°P-timi 50 Trial
Authors: Magnani Giulia , Morrow David A , Scirica Benjamin M , Sabatine Marc S , Murphy Sabina A , Bonaca Marc P
Published: April 2024

Background:
Oral antiplatelet (AP) therapy is broadly supported as preventive therapy for patients with established atherosclerotic vascular disease; however, emerging evidence for specific agents show heterogeneous outcomes by symptomatic vascular bed. Patterns of use may vary by symptomatic territory.

Methods:
We examined patterns of AP use at baseline in 26,449 stable outpatients randomized in the TRA 2° P-TIMI 50 trial including 17,779 with history of myocardial infarction (MI), 4,883 with history of ischemic stroke (CVD), and 3,787 with peripheral artery disease (PAD).

Results:
Overall 24,734 (94%) of patients were on aspirin (ASA). In the MI cohort 17448 (98%) were treated with aspirin and the majority (76%) were treated with dual AP therapy with aspirin and a thienopyridine (DAPT) (fig). Within the CVD group overall AP use was frequent (98%) with the majority on monotherapy (70%) with either ASA (54%) or thienopyrdine (16%) (fig). Of those on multi-agent therapy (28%) the combination of ASA and dipyridamole was more frequent then DAPT (19% vs 7%). Within the PAD group AP therapy was also frequent (97%) with a similar proportion on monotherapy (69%) with either ASA (60%) or thienopyridine (9%). In those on multi-agent therapy, DAPT was the most frequent (28%) followed by the combination of ASA and cilostazol (11%) (fig).

Conclusions:
Although atherosclerosis is a systemic disease and data supporting the use of antiplatelet therapy has often evaluated benefit broadly, in practice the distribution of agent and the intensity vary by symptomatic vascular territory. These patterns reflect emerging heterogeneity in outcomes trials evaluating specific therapies by symptomatic bed and support further evaluation of the risks and benefits in these specific populations.
Abstract 18731: Prevention of Protease 2a-Mediated Cleavage of Dystrophin Inhibits Disruption of the Sarcolemma and Enteroviral-Mediated Cardiomyopathy
Authors: Peter Angela K , Lim Byung-Kwan , Xiong Dingding , Narezkina Anya , Yung Aaron , Hwang Kyung-Kuk , Yajima Toshitaka , Chen Ju , Knowlton Kirk U
Published: April 2024

Introduction:
Coxsackievirus (CV) is a member of the enteroviral genus of the picornavirus family and is known to be an important cause of myocarditis and heart failure in children and adults. Enteroviral protease 2A cleaves the viral polyprotein and a small number of host cell proteins such as the cytoskeletal protein, dystrophin, and the eukaryotic translation initiation factor (eIF4G)-1 and -2. Genetic deficiency of dystrophin causes cardiomyopathy in Duchenne muscular dystrophy and increases susceptibility to enteroviral myocarditis. However, the importance of protease 2A-mediated cleavage of dystrophin and disruption of the sarcolemma is not known. We hypothesized that cleavage of dystrophin by protease 2A is important in viral propagation, enteroviral-mediated cytopathic effects, and the development of cardiomyopathy following enteroviral infection.

Methods and Results:
The current studies were designed to test whether inhibition of dystrophin cleavage alters CVB3-mediated myocarditis. In order to address this hypothesis, we knocked-in a mutation at the protease 2A-cleavage site of the dystrophin gene, thus inhibiting only the cleavage of dystrophin following CVB3 infection. Mice expressing cleavage-resistant dystrophin were less susceptible to CVB3 infection as indicated by a significant decrease in the cardiac virus titer eight days post-CVB3 infection. Sarcolemmal integrity, as measured by Evan’s blue dye uptake and Von Kossa staining, was also significantly improved in cleavage -resistant mice. In addition, myocarditis was decreased in infected knock-in mice compared to wild-type infected littermate controls. Also, prevention of dystrophin cleavage in protease 2A expressing transgenic mice markedly inhibited the protease 2A-induced myocytopathic effect.

Conclusions:
These findings indicate that disruption of the sarcolemma by protease 2A-mediated cleavage of dystrophin can have a critical role in viral propagation, enteroviral-mediated cytopathic effects, and the development of cardiomyopathy in control mice. These findings demonstrate that alterations in the dystrophin-glycoprotein complex which alter sarcolemmal integrity could contribute to susceptibility to virus infection.
Abstract 18739: Novel Protein Glycan Derived Marker of Systemic Inflammation is Associated With Incident Cardiovascular Disease
Authors: Akinkuolie Akintunde O , Buring Julie E , Ridker Paul M , Mora Samia
Published: April 2024

Background:
Enzymatically glycosylated proteins partake in multiple cellular processes, with variations in their concentration implicated in innate immunity and chronic inflammation. In addition, most inflammatory proteins are enzymatically glycosylated. GlycA is a novel nuclear magnetic resonance (NMR) biomarker whose signal originates from the N-acetyl groups of N-acetylglucosmine and N-acetylgalatosamine moieties of protein glycans. We tested the hypothesis that GlycA is related to incident CVD and compared it with high sensitivity C-reactive protein (hsCRP)

Method:
Baseline GlycA was quantified by NMR spectroscopy (LipoScience, NC) in 27 649 participants of the Women’s Health Study. A total of 1 651 cases of incident CVD events occurred during a median follow up of 17 years

Results:
GlycA correlated with LDL cholesterol (r = 0.17), HDL cholesterol (r = -0.27), triglycerides (r = 0.47), BMI (r = 0.41) and hsCRP (r = 0.61), all p<0.0001. Multivariable-adjusted Cox regression HRs (95% CIs) across increasing quartiles of GlycA for incident CVD were 1.00, 1.10 (0.92-1.30), 1.34 (1.14-1.58) and 1.64 (1.39-1.94), p trend <0.0001, similar in magnitude to the association of hsCRP with CVD (Table). The association of GlycA with CVD was attenuated but remained significant after additional adjustment for lipids (p-trend=0.0006). Further adjustment for hsCRP attenuated the association which was no longer statistically significant (p trend=0.33). In joint models examining combined levels of GlycA and hsCRP, CVD risk was highest when both GlycA and hsCRP were elevated: fully-adjusted HR 1.39 (1.13-1.71), p=0.002

Conclusion:
A novel protein glycan derived biomarker, GlycA, was associated with a graded increase in the risk of incident CVD events in this prospective study of initially healthy women in a manner similar to hsCRP. The association of GlycA with CVD was attenuated after adjusting for hsCRP, consistent with a possible role for protein glycans in inflammation and CVD
Abstract 18749: Avoidance of a Reload During the Therapeutic Shift From Clopidogrel to Ticagrelor in Patients With Acs Has No Influence on Residual Platelet Reactivity
Authors: Caiazzo Gianluca , De Rosa Salvatore , Torella Daniele , Micieli Mariella , Giampà Salvatore , Palella Eleonora , Spaccarotella Carmen , Mongiardo Annalisa , Gulletta Elio , Indolfi Ciro
Published: April 2024

Background:
Ticagrelor (TICA) was more efficient than clopidogrel (CLO) in preventing cardiovascular events after Acute Coronary Syndrome (ACS) in the PLATO trial. However, it was associated with a higher incidence of non-procedure related bleedings. Despite TICA therapy was always started with the administration of a loading dose in the PLATO trial, the loading dose could be unnecessary in patients with ongoing CLO therapy. Aim of the present study was to verify whether the administration of a loading dose is necessary to mantain the level of inhibition of aggregation during the switch from ongoing CLO to TICA therapy.

Methods and Results:
Fifty patients with ACS and on CLO treatment were randomly assigned to a starting dose of TICA of 90mg (Group 1) or 180mg (Group 2), on top of aspirin treatment. Platelet aggregation was measured using multiple electrode aggregometry (MEA) at 0, 2, 6, 24 and 72h after the switch, and verified through standard LTA aggregometry. No relevant difference in platelet aggregation between the two study arms was observed at baseline (p=0.256). Residual platelet aggregation measured using MEA was significantly reduced in both arms 2h after the first administration of TICA (both p<0.001). Interestingly, no difference in aggregation was found 2 hours after the switch to TICA (176 72 vs 181 60 AUmin, p=0.281). Similar findings were confirmed with LTA.

Conclusions:
Therapeutic switch from ongoing clopidogrel therapy to ticagrelor without administration of a loading dose is clinically safe and is not associated to a lower degree of inhibition in patients with ACS. Avoiding the loading dose could be associated to a lower bleeding risk while mantaining the same level of aggregation. Larger trials are needed to confirm data from our proof-of-concept study.