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2017 Cardiovascular Research Day Abstract Book

39 Effects of Molecular

39 Effects of Molecular Clock Component Deletion in Mouse Cardiomyocytes on Long QT Syndrome Phenotype Kaitlyn Samuels 1 • Elizabeth Schroder 1 • Tanya Seward 1 • Brian Delisle, PhD 1 1Physiology, University of Kentucky Undergraduate Cardiac excitability is affected by various genetic and environmental perturbations, which is often the cause of a multitude of human cardiac diseases. Specifically, this study explored the effects of the genetic knockout of the Bmal1 circadian transcription factor in mouse heart cells superimposed upon a congenital Scn5a sodium ion channel genetic mutation representative of long QT syndrome type 3 (LQT3) in humans. Changes in electrocardiographic (ECG) properties were evaluated to investigate the changes in cardiac excitability in these transgenic mice. There were a significantly higher number of cardiac arrhythmias after the Bmal1 gene knockout than before the knockout, specifically an increased number of RR-interval pauses. There was also a consistently slower heart rate after the Bmal1 gene knockout. Finally, there was increased slope factor between the RRinterval and QT-interval after the Bmal1 knockout than before the knockout. These findings are consistent with previous similar investigations and serve to help provide a better understanding of the pathophysiology associated with cardiac genetic mutations. 55

40 The Prognostic Role of Elevated Myeloperoxidase in Patients with Acute Coronary Syndrome: A Systematic Review and Meta-Analysis Mohamed Abo-Aly, MD 1 • Andrew kolodziej, MD 1 • Raphael Twerenbold, MD 1 • Christian Mueller, MD 1 • Ahmed Abdel-Latif, MD, PhD 1 1Division of cardiovascular medicine, Gill heart institution., University of Kentucky Postdoc Background: Many reports have shown the correlation between myeloperoxidase (MPO) and the pathogenesis of acute coronary syndrome (ACS). However, the prognostic role of MPO for major cardiac events or mortality in ACS patients has not been well studied. We sought to perform a systematic review and meta-analysis to examine the prognostic value of inpatient MPO level in patients presenting with ACS. Methods: PubMed and Cochrane databases were searched from 1975 to September 2017 for studies that investigated the prognostic value of serum MPO in patients with ACS. Studies should have dichotomized patients into a high MPO and a low MPO group, reported clinical outcomes according to the same cutoff value of MPO and followed up patients for at least 30 days to be eligible for enrollment. Data were analyzed using random-effects model to control heterogeneous reporting. Results: We retrieved 3896 studies for initial screening which yielded 14 studies including 9268 subjects with a median follow up of 8.7 ± 21.96 months for the final analysis. High serum MPO level significantly predicts the future risk of mortality (odds ratio [OR] 2.039; 95% confidence interval [CI]: 1.405-2.959; P=0.0176) and MACE (OR 1.42; 95% CI: 1.00-1.99; p=0.044). we also observed a string trend towards higher incidence of recurrent myocardial infarction (MI) in patients with high MPO level (OR 1.24; 95% CI: 0.99-1.54; p=0.054) in comparison to patients with low serum MPO. Conclusion: In this meta-analysis examining the long outcomes in ACS patients, high MPO levels were associated with worse clinical outcomes. These observations support the use of MPO as a novel clinical prognostic marker in patients with acute coronary syndrome. 56

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