The overall goal of this research is to advance our knowledge of the electrophysiological substrate and mechanism(s) of atrial fibrillation (AF) as evaluated at multiple endocardial recording sites. Statistical signal processing will be used to understand how the organizational structure of AF changes over time, with various interventions, and just prior to spontaneous termination. We posit that interventions which improve the degree of spatiotemporal organization of AF will reduce the endocardial atrial defibrillation theshhold (ADFT) and make AF more likely to spontaneously terminate, results which may have important implications for non-pharmacologic strategies of AF therapy. We will create two closed chest dog models AF by atrial enlargement and by rapid atrial pacing in order to show that shortening in total atrial effective refractory period (ERP) and increased spatial dispersion thereof leads to an increased propensity to sustain AF. We will show that vulnerability to induction of AF is related to regional dispersion of ERP. To show that regional and global spatiotemporal organization of AF are greater before spontaneous termination and successful defibrillation shocks, we will implement novel methods to measure parameters termed """"""""persistence,"""""""" and """"""""instantaneous disorganization"""""""" based on the spatial extent and period of time over which activation sequence remains nearly constant. We will also test the hypothesis that atrial pacing resulting in regional entrainment during AF, by improving the degree of spatiotemporal organization, significantly reduces the ADFT. Finally, we will create a series of long linear atrial lesions guided by intracardiac echocardiography and test the hypothesis that catheter-based long linear RF lesions placed in the right atrium will result in a)a more organized pattern of atrial fibrillation; and b) a lower ADFT.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL055227-03
Application #
2750503
Study Section
Surgery and Bioengineering Study Section (SB)
Project Start
1996-08-01
Project End
1999-07-31
Budget Start
1998-08-31
Budget End
1999-07-31
Support Year
3
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Sippensgroenewegen, A; Mlynash, M D; Roithinger, F X et al. (2001) Electrocardiographic analysis of ectopic atrial activity obscured by ventricular repolarization: P wave isolation using an automatic 62-lead QRST subtraction algorithm. J Cardiovasc Electrophysiol 12:780-90
SippensGroenewegen, A; Lesh, M D; Roithinger, F X et al. (2000) Body surface mapping of counterclockwise and clockwise typical atrial flutter: a comparative analysis with endocardial activation sequence mapping. J Am Coll Cardiol 35:1276-87
Roithinger, F X; Karch, M R; Steiner, P R et al. (1999) The spatial dispersion of atrial refractoriness and atrial fibrillation vulnerability. J Interv Card Electrophysiol 3:311-9
Roithinger, F X; Lesh, M D (1999) What is the relationship of atrial flutter and fibrillation? Pacing Clin Electrophysiol 22:643-54
Roithinger, F X; Steiner, P R; Goseki, Y et al. (1999) Electrophysiologic effects of selective right versus left atrial linear lesions in a canine model of chronic atrial fibrillation. J Cardiovasc Electrophysiol 10:1564-74
Roithinger, F X; Cheng, J; SippensGroenewegen, A et al. (1999) Use of electroanatomic mapping to delineate transseptal atrial conduction in humans. Circulation 100:1791-7
Roithinger, F X; Steiner, P R; Goseki, Y et al. (1999) Low-power radiofrequency application and intracardiac echocardiography for creation of continuous left atrial linear lesions. J Cardiovasc Electrophysiol 10:680-91
Roithinger, F X; SippensGroenewegen, A; Karch, M R et al. (1998) Organized activation during atrial fibrillation in man: endocardial and electrocardiographic manifestations. J Cardiovasc Electrophysiol 9:451-61
Roithinger, F X; Karch, M R; Steiner, P R et al. (1997) Relationship between atrial fibrillation and typical atrial flutter in humans: activation sequence changes during spontaneous conversion. Circulation 96:3484-91