PO-01-142 ACUTE ATRIAL DILATION INCREASES REFRACTORY PERIOD AND CONDUCTION ABNORMALITIES: EVIDENCE FROM IN-VIVO MAPPING AND IN-VITRO LIVING ATRIAL SLICES

Abstract

Atrial dilation shows strong clinical association with atrial fibrillation (AF) and its proarrhythmic nature is confirmed by various studies. However, previous (animal) models reproducing acute dilation yielded in conflicting effects on the functional refractory period (FRP). Shortcomings of previous studies included lack of in-human measurements, high-density mapping, atrial conduction characterization and titration of dilation. To evaluate the effect of acute atrial dilation on human atrial refractoriness and conduction with a two-way approach of in-vivo high-density mapping and in-vitro living atrial slices. Epicardial mapping with a 192-electrode array (inter-electrode distance 2.0 mm) was performed in 4 patients undergoing mitral valve surgery, without history of right atrial (RA) dilation and AF. Mapping was performed on the mid RA during baseline and overloaded conditions (echocardiographic RA diameter increase 10-20%) by positioning patients in Trendelenburg. Atrial FRP and conduction were evaluated with programmed extrastimulation, consisting of a S1-sequence with cycle length (CL) of 400ms followed by S2 stimuli of 300ms with decrements of 20ms. In addition, 23 living myocardial slices (LMS) (thickness: 300μm) were produced from RA left-over material from cardiac surgeries and cultured under electromechanical stimulation (diastolic preload 1mN, electrical stimulation 1.0Hz). These LMS were overloaded with 10–40% extra uniaxial lengthening for evaluation of FRP and early aftercontractions (EAC). FRP significantly increased during acute dilation both in in-vitro LMS (211±49 vs. 271±34ms, p=0.01) and during in-vivo electrophysiological mapping (255±30 vs. 280±23ms, p=0.042). FRP further increased with increasing dilation and EAC were more present in dilated LMS (Table 1). During acute dilation, S2 pacing (CL: 300ms) resulted in an increase in total activation time (TAT) (31 (29–39) vs. 67 (49–82) ms), conduction block (0.6 (0.0–3.0) vs. 12.9 (8.4-16.7)%) and total length of conduction block (2 (0–9) vs. 48 (21–72) mm). Moreover, the S2 stimulus with shortest coupling interval showed even more abnormalities in atrial conduction during dilation compared to baseline (Table 1). This first in-human study showed an unambiguous increase in atrial FRP and frequency-dependent conduction abnormalities during acute atrial dilation. These observations provide novel insights in the enhanced vulnerability for the development of AF in patients with dilated atria.Tabled 1Table 1In-vivo: EP mappingBaselineDilationRA Ø (cm)4.6 ± 1.05.6 ± 1.2CVP (mmHg)8 ± 418 ± 8FRP (ms)255 ± 30280 ± 23S1 400 msTAT (ms)34 (32 – 41)44 (40 – 52)CV (cm/s)85.5 (81.1 – 86.1)80.9 (77.7 – 83.8)CB (%)1.5 (1.1 – 2.1)3.1 (1.7 – 4.4)Length CB (mm)7 (5 – 9)16 (9 – 22)S2 300 msTAT (ms)31 (29 – 39)67 (49 – 82)CV (cm/s)82.1 (75.3 – 86.0)68.9 (61.6 – 79.8)CB (%)0.6 (0.0 – 3.0)11.7 (5.6 – 16.7)Length CB (mm)2 (0 – 9)48 (21 – 72)S2 with shortest coupling intervalTAT (ms)49 (41 – 61)82 (75 – 84)CV (cm/s)72.2 (67.0 – 78.3)66.7 (61.6 – 73.2)CB (%)6.0 (2.9 – 11.3)12.9 (8.4 – 16.7)Length CB (mm)30 (11 – 49)53 (33 – 72)In-vitro: LMSBaselineDilationAcute 20% (n=10)FRP (ms)211 ± 49271 ± 34EAC (%)0%50%Titration (n=13)10%20%30%40%FRP (ms)241 ± 46263 ± 68278 ± 63297 ± 75330 ± 79 Open table in a new tab