title: Whole heart action potential duration restitution properties in cardiac patients: a combined clinical and modelling study.
abstract: Steep action potential duration (APD) restitution has been shown to facilitate wavebreak and ventricular fibrillation. The global APD restitution properties in cardiac patients are unknown. We report a combined clinical electrophysiology and computer modelling study to: (1) determine global APD restitution properties in cardiac patients; and (2) examine the interaction of the observed APD restitution with known arrhythmia mechanisms. In 14 patients aged 52-85 years undergoing routine cardiac surgery, 256 electrode epicardial mapping was performed. Activation-recovery intervals (ARI; a surrogate for APD) were recorded over the entire ventricular surface. Mono-exponential restitution curves were constructed for each electrode site using a standard S1-S2 pacing protocol. The median maximum restitution slope was 0.91, with 27% of all electrode sites with slopes<0.5, 29% between 0.5 and 1.0, and 20% between 1.0 and 1.5. Eleven per cent of restitution curves maintained slope>1 over a range of diastolic intervals of at least 30 ms; and 0.3% for at least 50 ms. Activation-recovery interval restitution was spatially heterogeneous, showing regional organization with multiple discrete areas of steep and shallow slope. We used a simplified computer model of 2-D cardiac tissue to investigate how heterogeneous APD restitution can influence vulnerability to, and stability of re-entry. Our model showed that heterogeneity of restitution can act as a potent arrhythmogenic substrate, as well as influencing the stability of re-entrant arrhythmias. Global epicardial mapping in humans showed that APD restitution slopes were organized into regions of shallow and steep slopes. This heterogeneous organization of restitution may provide a substrate for arrhythmia.
authors.affiliation: Bioengineering Institute and Engineering Science, University of Auckland, New Zealand, and Department of Cardiology, University College Hospital, 16-18 Westmoreland Street, London W1G 8PH, UK.
authors.forename: Martyn P
authors.initials: MP
authors.lastname: Nash
authors.forename: Chris P
authors.initials: CP
authors.lastname: Bradley
authors.forename: Peter M
authors.initials: PM
authors.lastname: Sutton
authors.forename: Richard H
authors.initials: RH
authors.lastname: Clayton
authors.forename: Panny
authors.initials: P
authors.lastname: Kallis
authors.forename: Martin P
authors.initials: MP
authors.lastname: Hayward
authors.forename: David J
authors.initials: DJ
authors.lastname: Paterson
authors.forename: Peter
authors.initials: P
authors.lastname: Taggart
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D001022:Aortic Valve Insufficiency / Q000503:physiopathology; D001145:Arrhythmias, Cardiac / Q000209:etiology / Q000503:physiopathology; D018780:Body Surface Potential Mapping; D003198:Computer Simulation; D003327:Coronary Disease / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000503:physiopathology*; D006329:Heart Conduction System / Q000503:physiopathology; D006331:Heart Diseases / Q000188:drug therapy / Q000503:physiopathology*; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008955:Models, Cardiovascular