Published online before print May 6, 2002, doi: 10.1161/01.CIR.0000016826.62813.F5
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(Circulation. 2002;105:2672.)
© 2002 American Heart Association, Inc.
Basic Science Reports |
Dynamic Nature of Atrial Fibrillation Substrate During Development and Reversal of Heart Failure in Dogs
From the Departments of Medicine (K.S., Y.-F.S., J.-C.T., S.N.) and Pathology (T.-K.L.) and the Research Center (K.S., Y.-F.S., J.-C.T., S.N.), Montreal Heart Institute, and University of Montreal, Department of Pharmacology, McGill University (S.N.), Montreal, Canada.
Reprint requests to Stanley Nattel, MD, Montreal Heart Institute Research Center, 5000 Belanger St E, Montreal, Quebec, H1T 1C8, Canada. E-mail nattel{at}icm.umontreal.ca
Background— Clinical atrial fibrillation (AF) often results from pathologies that cause atrial structural remodeling. The reversibility of arrhythmogenic structural remodeling on removal of the underlying stimulus has not been studied systematically.
Methods and Results— Chronically instrumented dogs were subjected to 4 to 6 weeks of ventricular tachypacing (VTP; 220 to 240 bpm) to induce congestive heart failure (CHF), followed by a 5-week recovery period leading to hemodynamic normalization at 5-week recovery (Wk5rec). The duration of burst pacing–induced AF under ketamine/diazepam/isoflurane anesthesia increased progressively during VTP and recovered toward baseline during the recovery period, paralleling changes in atrial dimensions. However, even at full recovery, sustained AF could still be induced under relatively vagotonic morphine/chloralose anesthesia. Wk5rec dogs showed no recovery of CHF-induced atrial fibrosis (3.1±0.3% for controls versus 10.7±1.0% for CHF and 12.0±0.8% for Wk5rec dogs) or local conduction abnormalities (conduction heterogeneity index 1.8±0.1 in controls versus 2.3±0.1 in CHF and 2.2±0.2 in Wk5rec dogs). One week of atrial tachypacing failed to affect the right atrial effective refractory period significantly in CHF dogs but caused highly significant effective refractory period reductions and atrial vulnerability increases in Wk5rec dogs.
Conclusions— Reversal of CHF is followed by normalized atrial function and decreased duration of AF; however, fibrosis and conduction abnormalities are not reversible, and a substrate that can support prolonged AF remains. Early intervention to prevent fixed structural abnormalities may be important in patients with conditions that predispose to the arrhythmia.
Key Words: arrhythmias • remodeling • heart failure
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