title: Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart.
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.
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Neil T
authors.identifier: 0000-0002-4423-6547
authors.initials: NT
authors.lastname: Srinivasan
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Michele
authors.initials: M
authors.lastname: Orini
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Ron B
authors.initials: RB
authors.lastname: Simon
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Rui
authors.initials: R
authors.lastname: Providência
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Fakhar Z
authors.initials: FZ
authors.lastname: Khan
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Oliver R
authors.initials: OR
authors.lastname: Segal
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Girish G
authors.initials: GG
authors.lastname: Babu
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Richard
authors.initials: R
authors.lastname: Bradley
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Edward
authors.initials: E
authors.lastname: Rowland
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Syed
authors.initials: S
authors.lastname: Ahsan
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Chow
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and.
authors.forename: Martin D
authors.initials: MD
authors.lastname: Lowe
authors.affiliation: Institute of Cardiovascular Science, University College London, London, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Taggart
authors.affiliation: Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and Institute of Cardiovascular Science, University College London, London, United Kingdom d.lambiase@ucl.ac.uk.
authors.forename: Pier D
authors.initials: PD
authors.lastname: Lambiase
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000328:Adult; D004562:Electrocardiography; D004699:Endocardium / Q000502:physiology*; D005260:Female; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium; D016276:Ventricular Function
keywords: APD heterogeneity; dispersion of repolarization; human; restitution; whole heart