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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL032257-30
Application #
8694709
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Boineau, Robin
Project Start
1983-08-08
Project End
2018-04-30
Budget Start
2014-05-09
Budget End
2015-04-30
Support Year
30
Fiscal Year
2014
Total Cost
$561,306
Indirect Cost
$192,026
Name
Washington University
Department
Surgery
Type
Schools of Medicine
DUNS #
068552207
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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