Early Afterdepolarizations and Cardiac Arrhythmias

Overview

Journal Heart Rhythm

Publisher Elsevier

Specialty Cardiology & Vascular Diseases

Date 2010 Sep 28

PMID 20868774

Citations 189

Authors

James N Weiss

Alan Garfinkel

Hrayr S Karagueuzian

Peng-Sheng Chen

Zhilin Qu

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Proarrhythmic Lipid Inflammatory Mediators: Mechanisms in Obesity Arrhythmias.

Bahrami P, Aromolaran K, Aromolaran A J Cell Physiol. 2025; 240(2):e70012.

PMID: 39943721 PMC: 11822244. DOI: 10.1002/jcp.70012.

Mechanistic Relevance of Ventricular Arrhythmias in Heart Failure with Preserved Ejection Fraction.

Bahrami P, Aromolaran K, Aromolaran A Int J Mol Sci. 2025; 25(24.

PMID: 39769189 PMC: 11677834. DOI: 10.3390/ijms252413423.

Ventricular arrhythmia in congenital heart diseases with a systemic right ventricle.

Ladouceur M, Waldmann V, Bartoletti S, Chaix M, Khairy P Int J Cardiol Congenit Heart Dis. 2024; 13:100463.

PMID: 39712230 PMC: 11657340. DOI: 10.1016/j.ijcchd.2023.100463.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

Tzeis S, Gerstenfeld E, Kalman J, Saad E, Sepehri Shamloo A, Andrade J J Arrhythm. 2024; 40(6):1217-1354.

PMID: 39669937 PMC: 11632303. DOI: 10.1002/joa3.13082.

Mechanism of Arrhythmogenesis Driven by Early After Depolarizations in Cardiac Tissue.

Stein J, Greene D, Fenton F, Shiferaw Y bioRxiv. 2024; .

PMID: 39605738 PMC: 11601420. DOI: 10.1101/2024.11.14.623585.

References

Luo C, Rudy Y . A dynamic model of the cardiac ventricular action potential. II. Afterdepolarizations, triggered activity, and potentiation. Circ Res. 1994; 74(6):1097-113. DOI: 10.1161/01.res.74.6.1097. View

Tanskanen A, Greenstein J, ORourke B, Winslow R . The role of stochastic and modal gating of cardiac L-type Ca2+ channels on early after-depolarizations. Biophys J. 2004; 88(1):85-95. PMC: 1201453. DOI: 10.1529/biophysj.104.051508. View

Akar F, Rosenbaum D . Transmural electrophysiological heterogeneities underlying arrhythmogenesis in heart failure. Circ Res. 2003; 93(7):638-45. DOI: 10.1161/01.RES.0000092248.59479.AE. View

Volders P, Kulcsar A, Vos M, Sipido K, Wellens H, LAZZARA R . Similarities between early and delayed afterdepolarizations induced by isoproterenol in canine ventricular myocytes. Cardiovasc Res. 1997; 34(2):348-59. DOI: 10.1016/s0008-6363(96)00270-2. View

Waldo A, Camm A, deRuyter H, Friedman P, MacNeil D, Pauls J . Effect of d-sotalol on mortality in patients with left ventricular dysfunction after recent and remote myocardial infarction. The SWORD Investigators. Survival With Oral d-Sotalol. Lancet. 1996; 348(9019):7-12. DOI: 10.1016/s0140-6736(96)02149-6. View

Gray R, Jalife J, Panfilov A, Baxter W, Cabo C, Davidenko J . Nonstationary vortexlike reentrant activity as a mechanism of polymorphic ventricular tachycardia in the isolated rabbit heart. Circulation. 1995; 91(9):2454-69. DOI: 10.1161/01.cir.91.9.2454. View

Choi B, Burton F, Salama G . Cytosolic Ca2+ triggers early afterdepolarizations and Torsade de Pointes in rabbit hearts with type 2 long QT syndrome. J Physiol. 2002; 543(Pt 2):615-31. PMC: 2290501. DOI: 10.1113/jphysiol.2002.024570. View

Akar F, Yan G, Antzelevitch C, Rosenbaum D . Unique topographical distribution of M cells underlies reentrant mechanism of torsade de pointes in the long-QT syndrome. Circulation. 2002; 105(10):1247-53. DOI: 10.1161/hc1002.105231. View

Sato D, Xie L, Sovari A, Tran D, Morita N, Xie F . Synchronization of chaotic early afterdepolarizations in the genesis of cardiac arrhythmias. Proc Natl Acad Sci U S A. 2009; 106(9):2983-8. PMC: 2651322. DOI: 10.1073/pnas.0809148106. View

10.

dAlnoncourt C, Zierhut W, Bluderitz B . "Torsade de pointes" tachycardia. Re-entry or focal activity?. Br Heart J. 1982; 48(3):213-6. PMC: 481231. DOI: 10.1136/hrt.48.3.213. View

11.

Shilnikov A, Cymbalyuk G . Transition between tonic spiking and bursting in a neuron model via the blue-sky catastrophe. Phys Rev Lett. 2005; 94(4):048101. DOI: 10.1103/PhysRevLett.94.048101. View

12.

Lu H, Vlaminckx E, Van Ammel K, De Clerck F . Drug-induced long QT in isolated rabbit Purkinje fibers: importance of action potential duration, triangulation and early afterdepolarizations. Eur J Pharmacol. 2002; 452(2):183-92. DOI: 10.1016/s0014-2999(02)02246-x. View

13.

Channell P, Cymbalyuk G, Shilnikov A . Origin of bursting through homoclinic spike adding in a neuron model. Phys Rev Lett. 2007; 98(13):134101. DOI: 10.1103/PhysRevLett.98.134101. View

14.

Roden D . Clinical practice. Long-QT syndrome. N Engl J Med. 2008; 358(2):169-76. DOI: 10.1056/NEJMcp0706513. View

15.

Clancy C, Tateyama M, Liu H, Wehrens X, Kass R . Non-equilibrium gating in cardiac Na+ channels: an original mechanism of arrhythmia. Circulation. 2003; 107(17):2233-7. DOI: 10.1161/01.CIR.0000069273.51375.BD. View

16.

Peters N, Wit A . Myocardial architecture and ventricular arrhythmogenesis. Circulation. 1998; 97(17):1746-54. DOI: 10.1161/01.cir.97.17.1746. View

17.

Patterson E, Po S, Scherlag B, Lazzara R . Triggered firing in pulmonary veins initiated by in vitro autonomic nerve stimulation. Heart Rhythm. 2005; 2(6):624-31. DOI: 10.1016/j.hrthm.2005.02.012. View

18.

Tomaselli G, Zipes D . What causes sudden death in heart failure?. Circ Res. 2004; 95(8):754-63. DOI: 10.1161/01.RES.0000145047.14691.db. View

19.

Sridhar A, Nishijima Y, Terentyev D, Terentyeva R, Uelmen R, Kukielka M . Repolarization abnormalities and afterdepolarizations in a canine model of sudden cardiac death. Am J Physiol Regul Integr Comp Physiol. 2008; 295(5):R1463-72. PMC: 2584860. DOI: 10.1152/ajpregu.90583.2008. View

20.

Silva J, Rudy Y . Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve. Circulation. 2005; 112(10):1384-91. PMC: 1820744. DOI: 10.1161/CIRCULATIONAHA.105.543306. View