J-Wave Syndromes
Brian Foo
B.Sc. Life Sciences Student
Queen’s University
Canada
Road-Map
• Background
•Repolarization of heart tissue
• Physiology of J-wave syndromes
•Cellular Basis
•Arrhythmogenesis
• Classification
•Acquired
•Inherited
Background Information
Overview
• Repolarization of cardiac tissue
• Different repolarization patterns
within the heart
• ECG
Cardiac Repolarization
Ito: “transient outwards”
r repolarizing K+
Ica: Depolarizing inwards Ca+2
Ik : Repolarizing inwards K+
Ito
Ica
IK
Reviewed in Keating and Sanguinetti, 2001
Layers of the Heart
Exterior
Epicardium
Myocardium
vascularconcepts.net
Interior
Litovski and Antzelevitch, 1988
Endocardium
Differences in repolarization
Endocardium
Epicardium
Reviewed in Yan et al,. 2003
Differences in Repolarization
Reviewed in Yan et al,. 2003
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
J-Wave Physiology
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
J-Wave
• Excessive phase 1 hyperpolarization
Yan et al., 2003
Reviewed in Yan et al., 2003
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
Potential Consequences
Shortened AP
Antzelevitch and Yan, 2010
Arrhythmogenesis
• Re-entrant ventricular fibrillation
Area 1
Area 2
Antzlevitch and Yan, 2010
Classifications
Overview
• Inherited
•Brugada Syndrome (BS)
•Early Repolarization Syndrome (ERS)
• Acquired
•Myocardial Infarction
•Hypothermia
Inherited J-wave Syndromes
• Ion Channel Mutations
Gain of Function
Loss of Function
Antzelevitch and Yan, 2010
Brugada vs. ERS
Brugada
Location of Right
J-wave
precordial
leads (V1-V3)
ERS
Mid - left
precordial
leads (V4-V6)
Prognosis
Lower risk of
fibrillation
Phase 2
depression
High risk of
fibrillation
Proposed
Increased
Mechanism phase 1 repol.
Gussak and Antzelevitch 2000
Brugada Syndrome
• Increased Phase 1 repolarization
• Shortened action potential  re-entry
Potential for loss of
Phase 2 Ca+2 current
Gussak and Antzelevitch 2000
Brugada.org
Heterogeneous Repolarization
and risk of re-entry
Early Repol. Syndrome
• Decreased phase 2 Vm
• Creates transmural voltage gradient
without heterogeneous repolarization
Transmural voltage gradient
Brugada.org
Gussak and Antzelevitch 2000
Aquired J-Wave Syndromes
• Myocardial Infarction
• Hypothermia
Myocardial Injury
• Different epi and endo response to ischemia
Yan et al. 2004
Gilmour and Zipes, 1980; 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
Hypothermia
Yan, 1996
Patel et al. 1994; Antzelvitch and Yan, 1996
Summary
Cardiac Injury
(MI, Hypothermia)
Channel Defects
(Brugada, ERS)
Excessive Epicardial/
Myocardial Repolarization
Transmural
Voltage gradient
Heterogeneous
loss of Ica
Re-entry and
fibrillation
ECG Signs:
-J-Wave
-ST elevation
References
1.
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.