Journal
HEART RHYTHM
Volume 7, Issue 12, Pages 1891-1899Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.hrthm.2010.09.017
Keywords
Afterdepolarization; Arrhythmia; Chaos synchronization; Computer modeling; Nonlinear dynamics; Sudden cardiac death; Systems biology; Torsades de pointes; Triggered activity
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Funding
- National Institutes of Health/National Heart, Lung, and Blood Institute [P01-HL078931, R01-HL103662]
- Laubisch Endowment
- Kawata Endowment
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Early afterdepolarizations (EADs) are an important cause of lethal ventricular arrhythmias in long QT syndromes and heart failure, but the mechanisms by which EADs at the cellular scale cause arrhythmias such as polymorphic ventricular tachycardia (PVT) and torsades de pointes (TdP) at the tissue scale are not well understood. Here we summarize recent progress in this area, discussing (1) the ionic basis of EADs, (2) evidence that deterministic chaos underlies the irregular behavior of EADs, (3) mechanisms by which chaotic EADs synchronize in large numbers of coupled cells in tissue to overcome source-sink mismatches, (4) how this synchronization process allows EADs to initiate triggers and generate mixed focal reentrant ventricular arrhythmias underlying PVT and TdP, and (5) therapeutic implications.
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