Short-term hypertension is associated with the development of atrial fibrillation substrate: A study in an ovine hypertensive model

BACKGROUND Hypertension is frequently complicated by the development of atrial fibrillation (AF). However, the mechanisms of this link remain poorly understood. In addition, whether shortterm hypertension can result in a substrate for AF is not known. OBJECTIVE The purpose of this study was to characterize the atrial substrate predisposing to AF due to short-duration hypertension. METHODS Sixteen sheep were studied: 10 had induced hypertension for 7 +/- 4 weeks via the one-kidney, one-clip model, and six were controls. Cardiac magnetic resonance imaging was used to assess functional changes. Open-chest electrophysiological study was performed using a custom-made 128-electrode epicardial plaque applied to both right (RA) and left atria (LA), including the Bachmann's bundle, to determine effective refractory periods (ERPs) and conduction velocity at four pacing cycle lengths from six sites. Tissue specimens were harvested for structural analysis. RESULTS The hypertensive group demonstrated the following compared with controls: higher blood pressure (P <.0001), enlarged LA (P <.05), reduced LA ejection fraction (P <.05), uniformly higher mean ERP (P <.001), slower mean conduction velocity (P <.001), higher conduction heterogeneity index (P <.0001), greater AF inducibility (P = .03), and increased AF durations (P = .04). Picrosirius red staining of atrial tissues revealed increased interstitial fibrosis (P <.0001). There was also evidence of increased inflammatory cell infiltrates (P <.0001). CONCLUSION Short-duration hypertension is associated with significant atrial remodeling characterized by atrial enlargement/dysfunction, interstitial fibrosis, inflammation, slowed/heterogeneous conduction, increased ERP, and greater propensity for AF.