Abstract
The spatial variation in restitution properties in relation to varying stimulus site is poorly defined. This study aimed to investigate the effect of varying stimulus site on apicobasal and transmural activation time (AT), action potential duration (APD) and repolarization time (RT) during restitution studies in the intact human heart. Ten patients with structurally normal hearts, undergoing clinical electrophysiology studies, were enrolled. Decapolar catheters were placed apex to base in the endocardial right ventricle (RVendo) and left ventricle (LVendo), and an LV branch of the coronary sinus (LVepi) for transmural recording. S1-S2 restitution protocols were performed pacing RVendo apex, LVendo base, and LVepi base. Overall, 725 restitution curves were analyzed, 74% of slopes had a maximum slope of activation recovery interval (ARI) restitution (Smax) > 1 (P < 0.001); mean Smax = 1.76. APD was shorter in the LVepi compared with LVendo, regardless of pacing site (30-ms difference during RVendo pacing, 25-ms during LVendo, and 48-ms during LVepi; 50th quantile, P < 0.01). Basal LVepi pacing resulted in a significant transmural gradient of RT (77 ms, 50th quantile: P < 0.01), due to loss of negative transmural AT-APD coupling (mean slope 0.63 ± 0.3). No significant transmural gradient in RT was demonstrated during endocardial RV or LV pacing, with preserved negative transmural AT-APD coupling (mean slope -1.36 ± 1.9 and -0.71 ± 0.4, respectively). Steep ARI restitution slopes predominate in the normal ventricle and dynamic ARI; RT gradients exist that are modulated by the site of activation. Epicardial stimulation to initiate ventricular activation promotes significant transmural gradients of repolarization that could be proarrhythmic.
Highlights
Spatial variation of restitution in relation to varying stimulus site is poorly defined in the intact human heart
Smax was greater (Fig. 3A) in the LV endocardium (LVendo) compared with the RV endocardium (RVendo) and LVepi, and there was no significant difference in the mean slope between the RVendo and LVepi, irrespective of pacing site
The same pattern was noted with right ventricular (RV) apical and left ventricle (LV) basal pacing with steeper Smax throughout the LVendo compared with the RVendo and LVepi (Fig. 3, B and C)
Summary
Spatial variation of restitution in relation to varying stimulus site is poorly defined in the intact human heart. The spatial variation in restitution properties and AT-APD coupling in the intact human heart has largely only been studied in situations where global AT is relatively short, such as in sinus rhythm or right ventricular (RV) apical pacing, when early engagement of the Purkinje network occurs [52, 62] This homogenizes total AT, while maintaining a normal endocardial-to-epicardial activation sequence. Regional variations in APD have been shown in animal studies using ventricular wedge preparations, where transmural and apicobasal dispersion of APD and total RT have been demonstrated [3, 5, 31] Whether these regional variations in APD are present in the intact human myocardium, and whether they adapt to varying stimulus site to maintain negative AT-APD coupling, or are fixed to only homogenize total RT in response to the normal activation sequence, remains unclear. Our findings suggest that APD does not adapt when varying the stimulus site to the LV epicardium and basal LV endocardium, resulting in significant repolarization gradients, due to loss of negative AT-APD coupling [22, 36, 41, 45]
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