Arterial hypertension drives arrhythmia progression via specific structural remodeling in a porcine model of atrial fibrillation

Abstract

Background: Arterial hypertension (HT) contributes to progression of atrial fibrillation (AF) via unknown mechanisms.

Objective: We aimed to characterize electrical and structural changes accounting for increased AF stability in a large animal model of rapid atrial pacing (RAP)-induced AF combined with desoxycorticosterone acetate (DOCA)-induced HT.

Methods: Eighteen pigs were instrumented with right atrial endocardial pacemaker leads and custom-made pacemakers to induce AF by continuous RAP (600 beats/min). DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (AF+HT group); the other 9 animals served as controls (AF group). Final experiments included electrophysiology studies, endocardial electroanatomic mapping, and high-density mapping with epicardial multielectrode arrays. In addition, 3-dimensional computational modeling was performed.

Results: DOCA implantation led to secondary HT (median [interquartile range] aortic pressure 109.9 [100-137] mm Hg in AF+HT vs 82.2 [79-96] mm Hg in AF; P < .05), increased AF stability (55.6% vs 12.5% of animals with AF episodes lasting >1 hour; P < .05), concentric left ventricular hypertrophy, atrial dilatation (119 ± 31 cm² in AF+HT vs 78 ± 23 cm² in AF; P < .05), and fibrosis. Collagen accumulation in the AF+HT group was mainly found in non-intermyocyte areas (1.62 ± 0.38 cm³ in AF+HT vs 0.96 ± 0.3 cm³ in AF; P < .05). Left and right atrial effective refractory periods, action potential durations, endo- and epicardial conduction velocities, and measures of AF complexity were comparable between the 2 groups. A 3-dimensional computational model confirmed an increase in AF stability observed in the in vivo experiments associated with increased atrial size.

Conclusion: In this model of secondary HT, higher AF stability after 2 weeks of RAP is mainly driven by atrial dilatation.

Keywords: Arterial hypertension; Atrial dilatation; Atrial fibrillation; Atrial fibrosis; Electrical remodeling; Structural remodeling.