The highest incidence of atrial fibrillation (AF) in patients referred for cardiac surgery is seen in patients with mitral valve (MV) disease. Approximately one third of patients referred for MV surgery have AF. Two to 2.5 million Americans suffer from MV disease and this prevalence is expected to double in the next 20 years. The worldwide burden of MV disease is even greater, and it is the most common underlying etiology of AF in the developing world. The most common underlying pathology is mitral regurgitation (MR).The purpose of this proposed project is to characterize the chronic structural, electrical, and mechanical remodeling of the atria in chronic MR in order to optimize and improve the surgical treatment of patients with both MR and AF. To realize this goal, our laboratory has created a novel model to look at left atrial volume overload that is physiologically similar to MR and has the advantage of being reversible, obviating the confounding effects of corrective surgery. A shunt is made between the left atrial appendage and the left ventricle (LV). We will also use two novel non-invasive technologies: electrocardiographic imaging and late gadolinium enhanced MRI to define the fibrotic substrates and the effect this has on atrial activation in patients with MR and AF.
The specific aims are:
Specific Aim 1. Define the electrical and mechanical substrates for AF in our chronic canine MR model by characterizing the detailed biatrial electrophysiology with the use of optical mapping, and correlating our mapping data with the underlying structural changes identified both by late gadolinium- enhanced MRI and histology.
Specific Aim 2. Determine the degree and distribution of oxidative stress in the atria in our canine MR model. Define if the oxidative stress is originating in tissue, phagocytes or from both sources and then determine if the oxidative stress causes fibrosis by selectively inhibiting either one or both of these pathways.
Specific Aim 3. Define the electrophysiological remodeling in patients with MR by using both electrocardiographic imaging (ECGI) and intraoperative mapping during normal sinus rhythm and AF. This electrical remodeling will be correlated with the underlying fibrosis determined by late gadolinium enhanced MRI. Successful completion of these aims will help define the underlying mechanisms for AF in MR. Specifically, it will help identify patients with MR who are at greatest risk of developing AF and will explain why some patients with severe MR develop AF and some do not develop AF.

Public Health Relevance

This study will attempt to understand the cause of atrial fibrillation, a common irregular heart beat, in patients with a diseased heart valve. By understanding the cause of the atrial fibrillation, it will help provide a rationale for determining the appropriate timing of the surgery, and who should have an ablation of their atrial fibrillation when they have surgery to repair or replace their heart valve.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
Project #
Application #
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Sopko, George
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Washington University
Schools of Medicine
Saint Louis
United States
Zip Code
Khiabani, Ali J; Adademir, Taylan; Schuessler, Richard B et al. (2018) Management of Atrial Fibrillation in Patients Undergoing Coronary Artery Bypass Grafting: Review of the Literature. Innovations (Phila) 13:383-390
Musharbash, Farah N; Schill, Matthew R; Hansalia, Vivek H et al. (2018) Minimally Invasive Versus Full-Sternotomy Septal Myectomy for Hypertrophic Cardiomyopathy. Innovations (Phila) 13:261-266
Musharbash, Farah N; Schill, Matthew R; Sinn, Laurie A et al. (2018) Performance of the Cox-maze IV procedure is associated with improved long-term survival in patients with atrial fibrillation undergoing cardiac surgery. J Thorac Cardiovasc Surg 155:159-170
Ruaengsri, Chawannuch; Schill, Matthew R; Khiabani, Ali J et al. (2018) The Cox-maze IV procedure in its second decade: still the gold standard? Eur J Cardiothorac Surg 53:i19-i25
Schill, Matthew R; Melby, Spencer J; Speltz, Molly et al. (2017) Evaluation of a Novel Cryoprobe for Atrial Ablation in a Chronic Ovine Model. Ann Thorac Surg 104:1069-1073
Badhwar, Vinay; Rankin, J Scott; Damiano Jr, Ralph J et al. (2017) The Society of Thoracic Surgeons 2017 Clinical Practice Guidelines for the Surgical Treatment of Atrial Fibrillation. Ann Thorac Surg 103:329-341
Ishii, Yosuke; Schuessler, Richard B; Gaynor, Sydney L et al. (2017) Postoperative atrial fibrillation: The role of the inflammatory response. J Thorac Cardiovasc Surg 153:1357-1365
Lawrance, Christopher P; Henn, Matthew C; Miller, Jacob R et al. (2017) The Electrophysiologic Effects of Acute Mitral Regurgitation in a Canine Model. Ann Thorac Surg 103:1277-1284
Ad, Niv; Damiano Jr, Ralph J; Badhwar, Vinay et al. (2017) Expert consensus guidelines: Examining surgical ablation for atrial fibrillation. J Thorac Cardiovasc Surg 153:1330-1354.e1
Schill, Matthew R; Musharbash, Farah N; Hansalia, Vivek et al. (2017) Late results of the Cox-maze IV procedure in patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 153:1087-1094

Showing the most recent 10 out of 170 publications