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Whole heart action potential duration restitution properties in cardiac patients: a combined clinical and modelling
Martyn P Nash1, Chris P Bradley, Peter M Sutton
1Bioengineering Institute and Engineering Science, University of Auckland, New Zealand, and Department of Cardiology, University College Hospital, 16-18 Westmoreland Street, London W1G 8PH, UK.
Insights
Steep action potential duration (APD) restitution in cardiac patients is spatially heterogeneous, with regions of steep and shallow slopes. This variability may create a substrate for cardiac arrhythmias like ventricular fibrillation.
Area of Science:
- Cardiovascular Electrophysiology
- Cardiac Arrhythmia Mechanisms
- Computational Biology
Background:
- Steep action potential duration (APD) restitution is linked to wavebreak and ventricular fibrillation.
- Global APD restitution properties in cardiac patients remain largely unknown.
- Understanding these properties is crucial for arrhythmia management.
Purpose of the Study:
- To determine global APD restitution properties in cardiac patients.
- To investigate the interaction of APD restitution with known arrhythmia mechanisms.
- To explore the role of restitution heterogeneity in cardiac arrhythmias.
Main Methods:
- Combined clinical electrophysiology and computer modeling study.
- Epicardial mapping in 14 patients (age 52-85) during cardiac surgery.
- Activation-recovery intervals (ARI) recorded, restitution curves constructed, and computer models used to simulate re-entry.
Main Results:
- Median maximum restitution slope was 0.91, with significant spatial heterogeneity.
- 11% of sites had slopes >1 over at least 30 ms diastolic intervals.
- Heterogeneous APD restitution was observed, with organized regions of steep and shallow slopes.
Conclusions:
- Global epicardial mapping reveals spatially organized, heterogeneous APD restitution in cardiac patients.
- This heterogeneity, with regions of steep and shallow slopes, may serve as a substrate for cardiac arrhythmias.
- APD restitution heterogeneity influences vulnerability to and stability of re-entrant arrhythmias.
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.
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