Road-Map
• Background•Repolarization of heart tissue
• Physiology of J-wave syndromes•Cellular Basis
•Arrhythmogenesis
• Classification•Acquired
•Inherited
Overview
• Repolarization of cardiac tissue
• Different repolarization patterns within the heart
• ECG
Cardiac Repolarization
Ito
Ica
IK
Ito: “transient outwards” r repolarizing K+
Ica: Depolarizing inwards Ca+2
Ik : Repolarizing inwards K+
Reviewed in Keating and Sanguinetti, 2001
Layers of the Heart
Interior
Exterior
Litovski and Antzelevitch, 1988
vascularconcepts.net
Epicardium
Myocardium
Endocardium
ECG of Repolarization• ECG deflection reflects voltage differences
between layers of the heart
Mod. From Antzelvitch and Yan, 2003
Reviewed in Yan et al,. 2003
Overview
• Cellular Basis of J-wave syndromes
• ECG manifestations:•J-wave
•ST elevation
• Arrhythmogenesis•Re-enterant fibrilation
Cellular Basis
• Low Vm during repolarization phase of action potential
•Excessive phase 1 repolarization
•Insufficient phase 2 depolarization
ST Elevation• Excessive phase 1 repolarization
• Insufficient phase 2 depolarization
ST Elevation
Reviewed in Yan et al., 2003
Potential Consequences• If cell repolarizes too quickly, Ica will not
occur.•Leads to loss of phase 2 plateau and shortening of action
potential duration
Antzelevitch and Yan, 2010
Overview
• Inherited•Brugada Syndrome (BS)
•Early Repolarization Syndrome (ERS)
• Acquired•Myocardial Infarction
•Hypothermia
Inherited J-wave Syndromes
Antzelevitch and Yan, 2010
Gain of Function
Loss of Function
• Ion Channel Mutations
Brugada vs. ERS
Brugada ERS
Location of J-wave
Right precordial leads (V1-V3)
Mid - left precordial leads (V4-V6)
Prognosis High risk of fibrillation
Lower risk of fibrillation
Proposed Mechanism
Increased phase 1 repol.
Phase 2 depression
Gussak and Antzelevitch 2000
Brugada Syndrome• Increased Phase 1 repolarization
• Shortened action potential re-entry
Potential for loss ofPhase 2 Ca+2 current Heterogeneous Repolarization
and risk of re-entry
Brugada.org
Gussak and Antzelevitch 2000
Early Repol. Syndrome
• Decreased phase 2 Vm
• Creates transmural voltage gradient without heterogeneous repolarization
Transmural voltage gradient
Brugada.org
Gussak and Antzelevitch 2000
Myocardial Injury• Different epi and endo response to ischemia
Gilmour and Zipes, 1980; Yan et al. 2004
Yan et al. 2004
Hypothermia• Etiology unknown•Ion movement kinetics altered by temperature?
•Injury associated? (similar to MI)
Patel et al. 1994; Yan and Antzelevitch, 1996
SummaryCardiac Injury
(MI, Hypothermia)Channel Defects(Brugada, ERS)
TransmuralVoltage gradient
Heterogeneousloss of Ica
Re-entry andfibrillation
ECG Signs:-J-Wave-ST elevation
Excessive Epicardial/Myocardial Repolarization
References1. Antzelevitch C and Yan GX. Heart Rhythm 7: 549-558, 2010.
2. Gilmour RF, Jr. and Zipes DP. Circ Res 46: 814-825, 1980.
3. Gussak I, Antzelevitch C. J. Electrophysio 33(4): 299, 2000.
4. Hu D, Viskin S, Oliva A, Carrier T, Cordeiro JM, Barajas-Martinez H, Wu Y, Burashnikov E, Sicouri S, Brugada R, Rosso R, Guerchicoff A, Pollevick GD and Antzelevitch C. Heart Rhythm 4: 1072-1080, 2007.
5.
5. Keating MT and Sanguinetti MC. Cell 104: 569-580, 2001.
6. Litovsky SH and Antzelevitch C. Circ Res 62: 116-126, 1988.
7. Patel A, Getsos JP, Moussa G and Damato AN. Clin Cardiol 17: 273-276, 1994.
8. Yan GX and Antzelevitch C. Circulation 93: 372-379, 1996.
9. Yan GX, Joshi A, Guo D, Hlaing T, Martin J, Xu X and Kowey PR. Circulation 110: 1036-1041, 2004.
10. Yan GX, Lankipalli RS, Burke JF, Musco S and Kowey PR. J Am Coll Cardiol 42: 401-409, 2003.