Browsing by Author "Fedak, Paul W. M."

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    Adhesive-Enhanced Sternal Closure: Feasibility and Safety of Late Sternal Reentry
    (2017-05-29) Spooner, Aaron J.; Mewhort, Holly E. M.; DiFrancesco, Lisa M.; Fedak, Paul W. M.
    This clinical case report describes sternal reentry performed years after adhesive-enhanced sternal closure using Kryptonite bone cement. This report provides novel data on the late effects of this innovation. We observed that sternal reentry is feasible and safe. The adhesive did not weaken from biodegradation over a period of several years. There was no evidence of adherence to adjacent soft tissues or other nonbony deep mediastinal structures. Surgeons who receive patients who require redoing cardiac surgery after adhesive-enhanced closure with Kryptonite can be reassured that sternal reentry is safe and feasible.
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    Aorta-specific DNA methylation patterns in cell-free DNA from patients with bicuspid aortic valve-associated aortopathy
    (2021-07-28) Maredia, Ashna; Guzzardi, David; Aleinati, Mohammad; Iqbal, Fatima; Khaira, Arshroop; Madhu, Aiswarya; Wang, Xuemei; Barker, Alex J.; McCarthy, Patrick M.; Fedak, Paul W. M.; Greenway, Steven C.
    Abstract Background The dilation of the aorta that occurs as a consequence of a congenitally bicuspid aortic valve (BAV) is associated with a risk of dissection, aneurysm or rupture. With progressive aortopathy, surgery is often recommended, but current patient selection strategies have limitations. A blood-based assay to identify those who would most benefit from prophylactic surgery would be an important medical advance. In a proof-of-concept study, we sought to identify aorta-specific differentially methylated regions (DMRs) detectable in plasma cell-free DNA (cfDNA) obtained from patients undergoing surgery for BAV-associated aortopathy. Methods We used bioinformatics and publicly available human methylomes to identify aorta-specific DMRs. We used data from 4D-flow cardiac magnetic resonance imaging to identify regions of elevated aortic wall shear stress (WSS) in patients with BAV-associated aortopathy undergoing surgery and correlated WSS regions with aortic tissue cell death assessed using TUNEL staining. Cell-free DNA was isolated from patient plasma, and levels of candidate DMRs were correlated with aortic diameter and aortic wall cell death. Results Aortic wall cell death was not associated with maximal aortic diameter but was significantly associated with elevated WSS. We identified 24 candidate aorta-specific DMRs and selected 4 for further study. A DMR on chromosome 11 was specific for the aorta and correlated significantly with aortic wall cell death. Plasma levels of total and aorta-specific cfDNA did not correlate with aortic diameter. Conclusions In a cohort of patients undergoing surgery for BAV-associated aortopathy, elevated WSS created by abnormal flow hemodynamics was associated with increased aortic wall cell death which supports the use of aorta-specific cfDNA as a potential tool to identify aortopathy and stratify patient risk.
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    Surgical Application of ECM-Biomaterial Enhances Myocardial Recovery Following Myocardial Infarction
    (2016) Mewhort, Holly E. M.; Fedak, Paul W. M.; Giles, Wayne; Duff, Henry; Yong, Voon Wee
    Introduction: Ongoing improvements in the management of coronary artery disease continue to reduce mortality following myocardial infarction (MI), however, as a consequence the incidence of ischemic heart failure is on the rise. Healthy extracellular matrix (ECM) provides important cues that regulate cell function and survival. Dysregulation of the ECM following MI leads to cardiac fibrosis, left ventricular (LV) dilatation and heart failure. Here we assess whether ECM biology can be leveraged as a therapy to enhance myocardial recovery following MI. Methods and Results: Epicardial Infarct Repair (EIR), a novel bio-surgical procedure where a healthy ECM-biomaterial (CorMatrix®-ECM®, CorMatrix Cardiovascular Inc., GA, USA) is surgically applied to the epicardial surface of the heart post-MI, was evaluated. In a small animal permanent coronary artery ligation model we demonstrate that animals treated with ECM-biomaterial have improved myocardial function and attenuated LV remodeling compared to shams (ejection fraction (EF): 40.5±7.4% vs. 28.7±13.1%, respectively; p<0.001; LV end diastolic volume (LVEDV): 298.0±63.5μL vs. 373.7±78.8μL, respectively; p<0.0001). In order to determine whether this was the result of recovery of the infarcted myocardium or enhanced compensation by the remote myocardium we employed a large animal preclinical ischemia-reperfusion model and evaluated regional cardiac function by MRI demonstrating functional recovery of the infarcted myocardial territory, specifically infarcted myocardium otherwise defined as non-viable with reperfusion alone (change in regional myocardial contraction at 6-weeks: reperfusion+EIR: 28.6±14.0% vs. reperfusion alone: 4.2±13.5% wall thickening; p<0.05). In order to determine whether these structural and functional improvements are the consequence of passive biomechanical restraint or an active bio-inductive mechanism we compared EIR with active ECM-biomaterial versus inactivated (gluteraldehyde-fixed) ECM-biomaterial using our small animal permanent coronary artery ligation model. Animals treated with active ECM-biomaterial demonstrate improved cardiac function and attenuated structural remodeling when compared to inactivated ECM-biomaterial treated animals (EF: 40.5±7.4% vs. 32.7±9.3 %, respectively; p<0.001; LVEDV: 298.0±63.5μL vs. 341.2±48.4 μL, respectively; p<0.0001) as well as evidence of an active bio-inductive mechanism involving vasculogenesis. Conclusion: EIR with ECM-biomaterial attenuates adverse structural remodeling and improves functional recovery following MI through a bio-inductive mechanism involving vasculogenesis, demonstrating that healthy ECM biology can be leveraged to successfully treat MI.