136-04: Increased AF stability in a porcine model of rapid atrial pacing and arterial hypertension: Structural and electrical remodelling

Abstract

Introduction: Atrial fibrillation (AF) is the most common sustained arrhythmia in humans and is associated with an increased risk of stroke, morbidity and death. Arterial hypertension (HT) is found in 60–80% of AF patients, is an independent predictor of new-onset AF and contributes to AF progression via unknown mechanisms. We previously established a large animal model of rapid atrial pacing (RAP) induced atrial fibrillation combined with DOCA (desoxycorticosterone acetate) induced HT showing that HT increases AF stability. In this study, we aimed to investigate how arterial hypertension affects the progression of atrial fibrillation. Methods: 17 landrace pigs were implanted with custom made, telemetrically controllable pacemakers to induce AF. DOCA pellets were subcutaneously implanted in a subgroup of 9 animals (RAP + DOCA), the other 8 animals served as controls (RAP). Pacemakers were activated at a rate of 600/min two weeks prior to the final experiment which included transthoracic echocardiography, basic hemodynamic measurements, left and right atrial invasive electrophysiologic studies (measurement of atrial effective refractory periods – AERP – at S1 cycle lengths 400, 350, 300, 250 and 200ms), 3D electroanatomic mapping, high density epicardial multielectrode array mapping as well as histological analysis. Results: Both groups had comparable body weight (RAP + DOCA: 46.3 ± 6.1 kg; RAP: 44.9 ± 4.5; n.s.), cardiac output (4.6 ± 0.8 vs. 4.6 ± 1.2, n.s.), pulmonary arterial pressure (21.6 (16;27) vs. 24.5 (21;26), n.s.), left ventricular end diastolic pressure (13.1 ± 5.4 vs. 11.6 ± 4.8; n.s.) and left atrial pressure (7.6 ± 2.6 vs. 9.6 ± 4.6; n.s.). Animals in the RAP + DOCA group had significant arterial hypertension (109.9 (100,137) vs. 82.8 (79,96) mmHg, p < 0.05), concentric left ventricular hypertrophy (unchanged end-diastolic volume; end diastolic diameter of the intraventricular septum: 17(15,18) vs. 11.5(10,13) mm, p < 0.01), atrial dilatation (77.9 ± 23.4 vs. 119.1 ± 31.3 cm2, p < 0.01) and increased left (33.5 ± 8.4 vs. 24.9 ± 5.6 g, p < 0.05) and right (23.7 ± 2.9 vs. 19.4 ± 3.1 g, p < 0.05) atrial weights. AF duration after pacemaker activation was significantly higher in RAP + DOCA animals, while left and right atrial effective refractory periods at every measured S1 cycle length were unaltered. Epicardial multielectrode mapping showed increased conduction velocities on both atrial free walls (p < 0.05). Enhanced conduction velocity during closed chest 3D electroanatomic mapping of the whole atria in DOCA + RAP animals could be confirmed for the left, but not for the right atrium. Interestingly, this increased AF stability was not associated with increased AF complexity in both atria: mean AF cycle length, waves per cycle length, number of epicardial breakthroughs and mean conduction velocity during atrial fibrillation were unaltered. HT was associated with severe structural remodelling. Histologic evaluation showed biatrial cardiomyocyte hypertrophy (cross-section cardiomyocyte area: LA: 243.7 ± 41.8 vs. 174.4 ± 36.0 µm2, p < 0.01, RA: 271.6 (232,326) vs. 186.8(169,202) µm2, p < 0.01) as well as interstitial fibrosis (LA: 14.0 ± 2.2 vs. 8.5 ± 1.6 %, p < 0.001; RA: 14.4 ± 3.4 vs. 8.3 ± 1.5 %, p < 0.001). Conclusion: In this model of secondary hypertension, higher AF stability after two weeks of rapid atrial pacing was associated with both structural and electrical remodelling. Arterial hypertension triggers hypertrophic and profibrotic pathways which contribute to AF progression early in the disease. This underlines the importance of strict blood pressure control in patients with arterial hypertension to prevent progression of the disease.