Dynamic Nature of Atrial Fibrillation Substrate During Development and Reversal of Heart Failure in Dogs

Abstract

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 (Wk5 rec ). 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. Wk5 rec dogs showed no recovery of CHF-induced atrial fibrosis (3.1Ϯ0.3% for controls versus 10.7Ϯ1.0% for CHF and 12.0Ϯ0.8% for Wk5 rec dogs) or local conduction abnormalities (conduction heterogeneity index 1.8Ϯ0.1 in controls versus 2.3Ϯ0.1 in CHF and 2.2Ϯ0.2 in Wk5 rec 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 Wk5 rec 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.

2016 ESC Guidelines for the management of atrial fibrillation developed in collaboration with EACTS

“…U wielu pacjentów ten proces przebudowy strukturalnej następuje przed wystąpieniem AF [78]. Ponieważ część tej przebudowy strukturalnej jest nieodwracalna, pożądane wydaje się wczesne rozpoczynanie leczenia [87]. W tabeli 4 przedstawiono przegląd najważniejszych zmian patofizjologicznych w tkance przedsionków, które wiążą się z AF, w także wymieniono odpowiadające im stany kliniczne, które mogą się przyczyniać do tych zmian.…”

Atrial Ionic Remodeling Induced by Atrial Tachycardia in the Presence of Congestive Heart Failure

“…14 The interaction between CHF and ATinduced remodeling appears to depend on the CHF state, rather than the AF substrate per se, based on observations during recovery from CHF. After full hemodynamic recovery from experimental CHF, the AF substrate and associated interstitial fibrosis remain, 15 but CHF-induced ionic remodeling disappears 16 and AT-induced ERP changes become indistinguishable from those in the normal heart. 15…”

Effects of Antiarrhythmic Drugs on Fibrillation in the Remodeled Atrium

“…Atrial tachycardia alone for 7 days had no effect on CV, as previously reported. 4,15,16 Amiodarone significantly reduced CV in both the RA and LA ( Figure 5A), but its effects on CV were the same in the absence and presence of tachycardia remodeling. Dofetilide had no effect on CV ( Figure 5B), as expected.…”

“…Details of the model have been published previously. 11,12,14,15 Dogs were initially anesthetized with ketamine (5.3 mg/kg IV), diazepam (0.25 mg/kg IV), and halothane (1% to 2%). Unipolar pacing leads for ventricular and atrial pacing were inserted fluoroscopically into the right ventricular (RV) apex and the right atrial (RA) appendage.…”