The highest incidence of atrial fibrillation (AF) in patients referred for cardiac surgery is seen in patients with mitral valve (MV) disease. Approximately 30% 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 a novel reversible chronic animal model of mitral regurgitation (MR), with and without AF, to optimize and improve the surgical treatment of patients with MR and Aft 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 pulmonary veins and the left ventricle (LV).
The specific aims are:
Aim 1. To characterize the electrical, structural, and mechanical remodeling in an acute and chronic canine model of MR and to determine if eliminating the MR reverses these changes.
Aim 2. A. To determine the time course of the inducibility of AF, after the onset of MR and determine the combined effects of MR and AF on the substrates responsible for the initiation and maintenance of AF. B. Determine the effect of eliminating the MR on these substrates.
Aim 3. To characterize the electrical and structural remodeling in patients with MR, and to correlate these data with the experimental animal model. Successful completion of these aims will help elucidate the evolution of the substrate for AF in patients with MR. Because these are the most common AF patients who present for surgery, understanding the time course and interaction of the mechanically induced electrical remodeling, as well as its reversibility, will help provide a rationale for determining he appropriate timing of surgery and which patients require AF ablation in addition to their MV surgery. In those patients needing AF ablation, these studies may suggest a more rational ablation strategy.

Public Health Relevance

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

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
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Boineau, Robin
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Washington University
Schools of Medicine
Saint Louis
United States
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Lawrance, Christopher P; Henn, Matthew C; Damiano Jr, Ralph J (2016) Surgery for Atrial Fibrillation. Heart Fail Clin 12:235-43
Lancaster, Timothy S; Schill, Matthew R; Greenberg, Jason W et al. (2016) Potassium and Magnesium Supplementation Do Not Protect Against Atrial Fibrillation After Cardiac Operation: A Time-Matched Analysis. Ann Thorac Surg 102:1181-8
Lee, Anson M; Miller, Jacob R; Voeller, Rochus K et al. (2016) A Simple Porcine Model of Inducible Sustained Atrial Fibrillation. Innovations (Phila) 11:76-8
Damiano Jr, Ralph J; Lawrance, Christopher P; Saint, Lindsey L et al. (2016) Detection of Atrial Fibrillation After Surgical Ablation: Conventional Versus Continuous Monitoring. Ann Thorac Surg 101:42-7; discussion 47-8
Lawrance, Christopher P; Henn, Matthew C; Damiano Jr, Ralph J (2015) Surgical ablation for atrial fibrillation: techniques, indications, and results. Curr Opin Cardiol 30:58-64
Kazui, Toshinobu; Henn, Mathew C; Watanabe, Yoshiyuki et al. (2015) The impact of 6 weeks of atrial fibrillation on left atrial and ventricular structure and function. J Thorac Cardiovasc Surg 150:1602-8
Henn, Matthew C; Lancaster, Timothy S; Miller, Jacob R et al. (2015) Late outcomes after the Cox maze IV procedure for atrial fibrillation. J Thorac Cardiovasc Surg 150:1168-76, 1178.e1-2
Lawrance, Christopher P; Henn, Matthew C; Damiano Jr, Ralph J (2014) Surgery for atrial fibrillation. Cardiol Clin 32:563-71
Watanabe, Yoshiyuki; Weimar, Timo; Kazui, Toshinobu et al. (2014) Epicardial ablation performance of a novel radiofrequency device on the beating heart in pigs. Ann Thorac Surg 97:673-8
Lawrance, Christopher P; Henn, Matthew C; Miller, Jacob R et al. (2014) Comparison of the stand-alone Cox-Maze IV procedure to the concomitant Cox-Maze IV and mitral valve procedure for atrial fibrillation. Ann Cardiothorac Surg 3:55-61

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