A temporal window of vulnerability for development of atrial fibrillation with advancing heart failure.
OBJECTIVE
Heart failure (HF) is associated with development of AF and life-threatening ventricular tachycardia and fibrillation (VT/VF). Vulnerability to development of AF and VT/VF at different stages of HF and the underlying pathophysiological mechanisms are poorly defined. The present study was designed to determine the time-course of development of electrical and structural remodelling of the atria and ventricles, and their contribution to induction of AF and VT/VF in a canine model of HF.


RESULTS
Dogs were ventricular tachypaced (VTP) for 2-3 weeks or 5-6 weeks ('early' and 'late' HF, respectively). Electrophysiological studies were performed in isolated atrial and ventricular preparations and correlated with cardiac dimensions and haemodynamic parameters recorded in vivo. Vulnerability to programmed electrical stimulation-induced AF was greater in early vs. late stages of HF (78% vs. 38%). In contrast, VT/VF was inducible in late but not in early stages of HF (38% vs. 0%). The temporal distinction in atrial and ventricular arrhythmia susceptibility was associated with a much more rapid development of electrical and structural remodelling in atria. Vulnerability to AF developed following moderate electro-structural remodelling and waned with further progression to severe remodelling, which averted rapid atrial activation.


CONCLUSIONS
A temporal window of vulnerability for AF appears relatively early during development of VTP-induced HF in dogs, whereas VT/VF vulnerability is observed at more advanced stages of HF. These findings, if confirmed in humans, may have clinical implications with regard to prognosis and approach to therapy of patients with HF.
Masonic Medical Research Laboratory, Utica, NY, USA.
Alexander
A
Burashnikov
José M
JM
Di Diego
Serge
S
Sicouri
Michael Xavier
MX
Doss
Agapios
A
Sachinidis
Hector
H
Barajas-Martínez
Dan
D
Hu
Yoshino
Y
Minoura
N
N
Sydney Moise
Bruce G
BG
Kornreich
Liguo
L
Chi
Luiz
L
Belardinelli
Charles
C
Antzelevitch
D000818:Animals; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000209:etiology* / Q000503:physiopathology*; D015415:Biomarkers / Q000097:blood; D004195:Disease Models, Animal; D018450:Disease Progression; D004285:Dogs; D004452:Echocardiography; D004562:Electrocardiography; D006333:Heart Failure / Q000150:complications* / Q000000981:diagnostic imaging / Q000503:physiopathology*; D006439:Hemodynamics; D013997:Time Factors
D015415:Biomarkers
Atrial fibrillation; Fibrosis; Heart failure; Ventricular Fibrillation