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

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

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

Reviewed in Yan et al., 2003

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

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

Aquired J-Wave Syndromes

• Myocardial Infarction

• Hypothermia

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

Hypothermia

Patel et al. 1994; Antzelvitch and Yan, 1996

Yan, 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.