Abstract 14654: Does Pharmacological Ventricular Rate Control Mitigate AF-Induced Remodeling in the Absence of Tachycardiomyopathy?
Introduction: Atrial fibrillation (AF) causes electrical and structural remodeling (primarily fibrosis) that promotes AF progression. Pharmacological ventricular rate control is used to prevent tachycardiomyopathy, but whether it can directly interfere with AF-associated structural remodeling has never been tested. This study was designed to evaluate the effect of pharmacological ventricular rate control during AF on substrate progression in dog models.
Methods: Four groups of dogs (N=6/group) were studied: AT-P dogs: right atrial tachypacing at 600 beats/min (AT-P) to induce sustained AF for 3 weeks without other intervention; AT-P+D dogs: AT-P X 3 wks with diltiazem-CD 360 mg/day to achieve rate control; AT-P+ABL dogs: AT-P X 3 wks with AV node ablation and ventricular backup pacing (80 bpm); and non-paced Sham dogs.
Results: Ventricular response rate averaged 172±16 (mean ±SE), 156±10 and 142±6 beats/min on days 1, 7 and 21 in AT-P dogs, vs 102±9**, 105±8* and 99±8** respectively (**p<0.01 for each) in AT-P+D dogs. LVEF decreased slightly (from 55.8±1.3% at baseline to 52.4±2.7% in AT-P, P=NS; 45.2±2.0%* in AT-P+D, *P<0.05; and 51.0±2.8% in AT-P+ABL, P=NS). LA dimension increased slightly but significantly (from 20.2±0.6 mm at baseline to 23.3±1.3 mm* in AT-P, 23.4±1.0 mm* in AT-P+D and 23.1±0.7 mm* in AT-P+ABL). At terminal open chest study, while overall conduction velocity (CV) was not significantly different (86±2 cm/sec in AT-P, 91±7 cm/sec in in AT-P+D, 87±3 cm/sec in AT-P+ABL and 96±6 cm/sec in Sham group), CV heterogeneity (reflecting local conduction slowing) was greater in AT-P (4.1±0.4) vs other groups: 2.2±0.2* in AT-P+D, 2.5±0.1* in AT-P+ABL and 2.6±0.3* in Sham group. Atrial ERP was reduced vs Sham (115 ±10 ms) in all tachypaced groups: 51±4** ms in AT-P, 82±7** ms AT-P+D, 58±4** ms ATP+ABL. Mean duration of AF induced by burst pacing was greater in AT-P (1065±258 sec) vs AT-P+D (229±77** sec), AT-P+ABL (378±130* sec) and Sham (45±8** sec). LA Collagen-1 mRNA expression was significantly greater in AT-P (19.0±3.3 A.U.) vs AT-P+D (6.7±0.3 A.U.*).
Conclusions: Pharmacological rate control prevents progression of the AF substrate due to structural remodeling. This is a novel consideration in the use and targeting of rate control therapy.
Author Disclosures: A.K. Saeid: None. S. Nattel: None.
- © 2014 by American Heart Association, Inc.