PMID- 27371682 OWN - NLM STAT- MEDLINE DCOM- 20170626 LR - 20200930 IS - 1522-1539 (Electronic) IS - 0363-6135 (Print) IS - 0363-6135 (Linking) VI - 311 IP - 3 DP - 2016 Sep 1 TI - Ventricular stimulus site influences dynamic dispersion of repolarization in the intact human heart. PG - H545-54 LID - 10.1152/ajpheart.00159.2016 [doi] AB - 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. CI - Copyright (c) 2016 the American Physiological Society. FAU - Srinivasan, Neil T AU - Srinivasan NT AUID- ORCID: 0000-0002-4423-6547 AD - 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. FAU - Orini, Michele AU - Orini M AD - 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. FAU - Simon, Ron B AU - Simon RB AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Providencia, Rui AU - Providencia R AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Khan, Fakhar Z AU - Khan FZ AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Segal, Oliver R AU - Segal OR AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Babu, Girish G AU - Babu GG AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Bradley, Richard AU - Bradley R AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Rowland, Edward AU - Rowland E AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Ahsan, Syed AU - Ahsan S AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Chow, Anthony W AU - Chow AW AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Lowe, Martin D AU - Lowe MD AD - Department of Cardiac Electrophysiology, The Barts Heart Center, St Bartholomew's Hospital, London, United Kingdom; and. FAU - Taggart, Peter AU - Taggart P AD - Institute of Cardiovascular Science, University College London, London, United Kingdom. FAU - Lambiase, Pier D AU - Lambiase PD AD - 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. LA - eng GR - FS/14/9/30407/British Heart Foundation/United Kingdom GR - G0901819/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20160701 PL - United States TA - Am J Physiol Heart Circ Physiol JT - American journal of physiology. Heart and circulatory physiology JID - 100901228 SB - IM MH - Action Potentials/*physiology MH - Adult MH - Electrocardiography MH - Endocardium/*physiology MH - Female MH - Heart/*physiology MH - Heart Conduction System/*physiology MH - *Heart Ventricles MH - Humans MH - Male MH - Middle Aged MH - Myocardium MH - *Ventricular Function PMC - PMC5142177 OTO - NOTNLM OT - APD heterogeneity OT - dispersion of repolarization OT - human OT - restitution OT - whole heart EDAT- 2016/07/03 06:00 MHDA- 2017/06/27 06:00 PMCR- 2016/07/01 CRDT- 2016/07/03 06:00 PHST- 2016/02/18 00:00 [received] PHST- 2016/06/29 00:00 [accepted] PHST- 2016/07/03 06:00 [entrez] PHST- 2016/07/03 06:00 [pubmed] PHST- 2017/06/27 06:00 [medline] PHST- 2016/07/01 00:00 [pmc-release] AID - ajpheart.00159.2016 [pii] AID - H-00159-2016 [pii] AID - 10.1152/ajpheart.00159.2016 [doi] PST - ppublish SO - Am J Physiol Heart Circ Physiol. 2016 Sep 1;311(3):H545-54. doi: 10.1152/ajpheart.00159.2016. Epub 2016 Jul 1.