1. J-Wave Syndromes Brian Foo B.Sc. Life Sciences Student Queen’s University Canada

2. Road-Map Background Repolarization of heart tissue Physiology of J-wave syndromes Cellular Basis Arrhythmogenesis Classification Acquired Inherited

3. Background Information

4. Overview Repolarization of cardiac tissue Different repolarization patterns within the heart ECG

5. Cardiac Repolarization I to I ca IKIK I to : “transient outwards” r repolarizing K + I ca : Depolarizing inwards Ca +2 I k : Repolarizing inwards K + Reviewed in Keating and Sanguinetti, 2001

6. Layers of the Heart Interior Exterior Litovski and Antzelevitch, 1988 vascularconcepts.net Epicardium Myocardium Endocardium

7. Differences in repolarization Endocardium Epicardium Reviewed in Yan et al,. 2003

8. Differences in Repolarization Reviewed in Yan et al,. 2003

9. 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

10. J-Wave Physiology

11. Overview Cellular Basis of J-wave syndromes ECG manifestations: J-wave ST elevation Arrhythmogenesis Re-enterant fibrilation

12. Cellular Basis Low V m during repolarization phase of action potential Excessive phase 1 repolarization Insufficient phase 2 depolarization

13. J-Wave Excessive phase 1 hyperpolarization Reviewed in Yan et al., 2003 Yan et al., 2003

14. ST Elevation Excessive phase 1 repolarization Insufficient phase 2 depolarization ST Elevation Reviewed in Yan et al., 2003

15. Potential Consequences If cell repolarizes too quickly, I ca will not occur. Leads to loss of phase 2 plateau and shortening of action potential duration Antzelevitch and Yan, 2010

16. Potential Consequences Shortened AP Antzelevitch and Yan, 2010

17. Arrhythmogenesis Re-entrant ventricular fibrillation Area 1 Area 2 Antzlevitch and Yan, 2010

18. Classifications

19. Overview Inherited Brugada Syndrome (BS) Early Repolarization Syndrome (ERS) Acquired Myocardial Infarction Hypothermia

20. Inherited J-wave Syndromes Antzelevitch and Yan, 2010 Gain of Function Loss of Function Ion Channel Mutations

21. Brugada vs. ERS BrugadaERS Location of J-wave Right precordial leads (V1-V3) Mid - left precordial leads (V4-V6) PrognosisHigh risk of fibrillation Lower risk of fibrillation Proposed Mechanism Increased phase 1 repol. Phase 2 depression Gussak and Antzelevitch 2000

22. Brugada Syndrome Increased Phase 1 repolarization Shortened action potential  re-entry Potential for loss of Phase 2 Ca +2 current Heterogeneous Repolarization and risk of re-entry Brugada.org Gussak and Antzelevitch 2000

23. Early Repol. Syndrome Decreased phase 2 V m Creates transmural voltage gradient without heterogeneous repolarization Transmural voltage gradient Brugada.org Gussak and Antzelevitch 2000

24. Aquired J-Wave Syndromes Myocardial Infarction Hypothermia

25. Myocardial Injury Different epi and endo response to ischemia Gilmour and Zipes, 1980; Yan et al. 2004 Yan et al. 2004

26. Hypothermia Etiology unknown Ion movement kinetics altered by temperature? Injury associated? (similar to MI) Patel et al. 1994; Yan and Antzelevitch, 1996

27. Hypothermia Patel et al. 1994; Antzelvitch and Yan, 1996 Yan, 1996

28. Summary Cardiac Injury (MI, Hypothermia) Channel Defects (Brugada, ERS) Transmural Voltage gradient Heterogeneous loss of I ca Re-entry and fibrillation ECG Signs: -J-Wave -ST elevation Excessive Epicardial/ Myocardial Repolarization

29. 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.