Contribution of fibrosis and the autonomic nervous system to atrial fibrillation electrograms in heart failure.
BACKGROUND
Fibrotic and autonomic remodeling in heart failure (HF) increase vulnerability to atrial fibrillation (AF). Because AF electrograms (EGMs) are thought to reflect the underlying structural substrate, we sought to (1) determine the differences in AF EGMs in normal versus HF atria and (2) assess how fibrosis and nerve-rich fat contribute to AF EGM characteristics in HF.


RESULTS
AF was induced in 20 normal dogs by vagal stimulation and in 21 HF dogs (subjected to 3 weeks of rapid ventricular pacing at 240 beats per minute). AF EGMs were analyzed for dominant frequency (DF), organization index, fractionation intervals (FIs), and Shannon entropy. In 8 HF dogs, AF EGM correlation with underlying fibrosis/fat/nerves was assessed. In HF compared with normal dogs, DF was lower and organization index/FI/Shannon entropy were greater. DF/FI were more heterogeneous in HF. Percentage fat was greater, and fibrosis and fat were more heterogeneously distributed in the posterior left atrium than in the left atrial appendage. DF/organization index correlated closely with %fibrosis. Heterogeneity of DF/FI correlated with the heterogeneity of fibrosis. Autonomic blockade caused a greater change in DF/FI/Shannon entropy in the posterior left atrium than left atrial appendage, with the decrease in Shannon entropy correlating with %fat.


CONCLUSIONS
The amount and distribution of fibrosis in the HF atrium seems to contribute to slowing and increased organization of AF EGMs, whereas the nerve-rich fat in the HF posterior left atrium is positively correlated with AF EGM entropy. By allowing for improved detection of regions of dense fibrosis and high autonomic nerve density in the HF atrium, these findings may help enhance the precision and success of substrate-guided ablation for AF.
Feinberg Cardiovascular Research Institute, Division of Cardiology, Department of Medicine, Northwestern University-Feinberg School of Medicine, Chicago, IL 60611, USA.
Hemantha
H
Koduri
Jason
J
Ng
Ivan
I
Cokic
Gary L
GL
Aistrup
David
D
Gordon
J Andrew
JA
Wasserstrom
Alan H
AH
Kadish
Richard
R
Lee
Rod
R
Passman
Bradley P
BP
Knight
Jeffrey J
JJ
Goldberger
Rishi
R
Arora
D000273:Adipose Tissue / Q000473:pathology; D018674:Adrenergic Antagonists / Q000494:pharmacology; D000818:Animals; D020517:Atrial Appendage / Q000294:innervation / Q000473:pathology; D001281:Atrial Fibrillation / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D016275:Atrial Function / Q000187:drug effects; D017763:Autonomic Denervation / Q000379:methods; D001341:Autonomic Nervous System / Q000187:drug effects / Q000503:physiopathology*; D002304:Cardiac Pacing, Artificial; D004195:Disease Models, Animal; D004285:Dogs; D022062:Electrophysiologic Techniques, Cardiac; D005355:Fibrosis; D006325:Heart Atria / Q000294:innervation / Q000473:pathology; D006333:Heart Failure / Q000150:complications* / Q000175:diagnosis / Q000473:pathology / Q000503:physiopathology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011237:Predictive Value of Tests
D018674:Adrenergic Antagonists; D018727:Muscarinic Antagonists