Abstract 2618: Hypertension and Atrial Fibrillation: A Long Term Study of Remodeling in a Conscious Ovine Model
Introduction Hypertension accounts for more atrial fibrillation (AF) than any other predisposing factors. In the evaluation of AF substrates in hypertension, the time course of electrical, functional and structural remodeling remains unknown.
Methods A total of 32 sheep (54±9kg) were studied: 21 had induced hypertension with the “one kidney-one clip” model while 11 were controls. Bilateral thoracotomy was performed to implant a custom-made 128-electrode epicardial plaque over both right (RA) and left atria (LA) to facilitate weekly electrophysiological study over 15 weeks. Atrial structural and functional analyses were performed at 5, 10 and 15 weeks of hypertension via picrosirius red stains and cardiac magnetic resonance imaging respectively.
Results The hypertensive group developed a progressive increase in mean arterial pressure over 15 weeks (78±7 to 125±9mmHg; p<0.0001). Progressive bi-atrial hypertrophy (RA: 16±3 to 19±2g, LA: 21±4 to 30±5g; p=0.003); LA dysfunction (Ejection fraction: 33.4±2.9 to 28.3±0.8%; p<0.05) and greater AF inducibility (2±4 to 20±16%; p=0.003) were seen early from 5 weeks of hypertension. Significant conduction slowing (0.92±0.08 to 0.80±0.13m/s; p<0.001) with increased heterogeneity index (1.08±0.20 to 1.87±0.51; p<0.001) along with increased interstitial fibrosis (2.6±1 to 5.2±2.7%; p<0.001) and longer AF durations (3±4 to 30±38s; p=0.04) were only more evident from 10 weeks of hypertension. Mean effective refractory periods were uniformly higher at all time points (p=0.0004) but with no observable trend.
Conclusions Atrial enlargement with reduction in function occurs early during the development of HT together with greater AF inducibility. Atrial fibrosis with its consequent slowed/heterogeneous conduction occurs later in the remodeling cascade leading to more sustained AF. Anti-hypertensive treatment at the opportune time may prevent formation of substrate capable of maintaining AF.