Left versus right atrial difference in dominant frequency, K+ channel transcripts, and fibrosis in patients developing atrial fibrillation after cardiac surgery

Swartz, Michael F.; Fink, Gregory W.; Lutz, Charles J.; Taffet, Steven M.; Berenfeld, Omer; Vikstrom, Karen L.; Kasprowicz, Kimberly; Bhatta, Luna; Puskas, Ferenc; Kalifa, Jérôme; Jalife, José

doi:10.1016/j.hrthm.2009.06.018

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Volume 6, Issue 10 , Pages 1415-1422, October 2009

Left versus right atrial difference in dominant frequency, K⁺ channel transcripts, and fibrosis in patients developing atrial fibrillation after cardiac surgery

Michael F. Swartz, MS
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York
- Department of Surgery, State University of New York Upstate Medical University, Syracuse, New York
Gregory W. Fink, MD
- Department of Surgery, State University of New York Upstate Medical University, Syracuse, New York
Charles J. Lutz, MD
- Department of Surgery, State University of New York Upstate Medical University, Syracuse, New York
Steven M. Taffet, PhD
- Department of Microbiology, State University of New York Upstate Medical University, Syracuse, New York
Omer Berenfeld, PhD
- Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan
Karen L. Vikstrom, PhD
- Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan
Kimberly Kasprowicz, MS
- Department of Anesthesia, State University of New York Upstate Medical University, Syracuse, New York
Luna Bhatta, MD
- Department of Medicine, State University of New York Upstate Medical University, Syracuse, New York
Ferenc Puskas, MD, PhD
- Department of Anesthesiology, University of Colorado at Denver, Denver, Colorado
Jérôme Kalifa, MD, PhD
- Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan
José Jalife, MD, FHRS
- Department of Pharmacology, State University of New York Upstate Medical University, Syracuse, New York
- Center for Arrhythmia Research, University of Michigan, Ann Arbor, Michigan
- Address reprint requests and correspondence: José Jalife, M.D., Center for Arrhythmia Research, University of Michigan, 5025 Venture Drive, Ann Arbor, Michigan 48108

Received 16 January 2009; accepted 12 June 2009. published online 19 June 2009.

Background

The development of atrial fibrillation (AF) after cardiac surgery is associated with adverse outcomes; however, the mechanism(s) that trigger and maintain AF in these patients are unknown.

Objective

The purpose of this study was to test our hypothesis that postoperative AF is maintained by high-frequency sources in the left atrium (LA) resulting from ion channel and structural features that differ from the right atrium (RA).

Methods

Forty-four patients with no previous history of AF who underwent cardiac surgery consented to LA and RA biopsies. Histologic sections evaluated fatty infiltration, fibrosis, and iron deposition; quantitative reverse transcription–polymerase chain reaction (RT-PCR) assessed ion channel expression. In a subset of 27 patients, LA and RA unipolar recording leads were also placed. In patients who developed AF, the dominant frequency (DF) for each lead was calculated using fast Fourier transform.

Results

DFs during AF were LA 6.26 ± 0.8 Hz, RA 4.56 ± 0.7 Hz (P <.01). RT-PCR revealed LA-to-RA differences in mRNA abundance for Kir2.3 (1.8:1) and Kir3.4 (2.3:1). While LA fibrosis was greater in patients developing AF compared with those remaining in normal sinus rhythm (10.8% ± 11% vs. 3.8% ± 3.5%; P = .03), the amount of LA fibrosis inversely correlated with the LA DF.

Conclusions

This is the first demonstration of LA-to-RA frequency differences during postoperative AF, which are associated with LA-to-RA differences in mRNA levels for potassium channel proteins and LA fibrosis. These results strongly suggest that sources of AF after cardiac surgery are located in the LA and are stabilized by LA fibrosis.

Keywords: Fibrillation, Electrophysiology, Fourier analysis, Cardiac surgery, Fibrosis