J Wave Syndromes. Osama Diab Lecturer of Cardiology Ain Shams University

Transcription

1 J Wave Syndromes Osama Diab Lecturer of Cardiology Ain Shams University

2 J Wave Syndromes Group of electric disorders characterized by > 1 mm elevation of the J point or prominent J wave with or without ST elevation J point J wave

3 Group of electric disorders sharing common mechanisms of arrhythmogenicity, one of which may be variant of the other Early repolarization Brugada J wave syndromes Hypothermia STEMI

4 Phase 1 of AP (Ito) Responsible for the AP notch Transient outward K current (Ito) Na current 1 0 K + Na + Ca ATP-sensitive K ch AC-sensitive K ch K + 3 K + 4 Delayed rectifier K ch

5 Epicardium Epicardium Endocardium Endocardium ECG

6 Epicardium Epicardium Endocardium Endocardium ECG

7 J wave syndromes (> 1 mm elevation of J point + ST elevation) Duration and magnitude of Endo to epicardiat gradient determines the J point/st segment elevation Epicardium Endocardium ECG Osborn Hypothermia Early repolarization STEMI Brugada

8 Propagation of the dome phase 2 reentry Endocardium Epicardium Yan GX, Lankipalli RS, Burke JF, Musco S, Kowey PR. Ventricular repolarization components on the electrocardiogram: cellular basis and clinical significance. J Am Coll Cardiol. 2003;42:

9 Propagation of the dome phase 2 reentry

10 Vagal stimulation/bradycardia/pauses + Ca ++ Vagus Isoprenaline K + ERS Yan GX, Lankipalli RS, Burke JF, Musco S, Kowey PR. Ventricular repolarization components on the electrocardiogram: cellular basis and clinical significance. J Am Coll Cardiol. 2003;42:

11 Magnitude of Na + current Normally Cell memb + Na + channels L- Ca ++ channels

12 Early closure of Na channels Slow activation of L-Ca channels prominent notch SCN5A Failed activation of L-Ca channels loss of AP dome Mutation Na channel blockers Free radicals LPC Cell memb Na + channels L- Ca ++ channels

13 Slow L-Ca ++ channel activation CACNA1C- CACNB2b gene mutation - Cell memb + Na + channels L- Ca ++ channels

14 Increased transient outward K + current (Ito) Ito gain of function mutation K + KCNE3- KCND3 gene mutation Regional loss of dome K + Giudicessi JR, et al. Transient Outward Current (Ito) Gain-of-Function Mutations in the KCND3-Encoded Kv4.3 Potassium Channel and Brugada Syndrome. Heart Rhythm (2011). Delpón E, et al. Functional Effects of KCNE3 Mutation and its Role in the Development of Brugada Syndrome. Circ Arrhythm Electrophysiol. 2008; 1(3):

15 Hypothermia J (Osborn) wave

16 BS and ERS can be considered to represent a continuous spectrum of the phenotypic expression of gene mutations Antzelevitch C, et al. J Wave Syndromes. Heart Rhythm April; 7(4):

17 Brugada like or ERS? J wave Syndrome

18 Aizawa Y, Tamura M, Chinushi M, et al. Idiopathic ventricular fibrillation and bradycardia-dependent intraventricular block. Am Heart J. 1993;126:

19 Patient with idiopathic VF (the bottom ECG was taken during sleep)

20 Brugada syndrome causes 4 12% of all SCDs, and up to 20% of SCDs without identifiable structural abnormalities Antzelevitch C, Brugada P, Brugada J, et al., Brugada syndrome: A decade of progress. Circ, Res 2002;91(12):

21 The ER pattern has long been considered to be a benign ECG manifestation that is more commonly seen in young healthy men and athletes Occurs in 5% of population

22 Haissaguerre and co-workers compared 206 subjects with IVF to 412 healthy controls and demonstrated that an ER pattern was in 31% of subjects with IVF vs 5% of controls (P<0.001). Patients with IVF who had the ER pattern were more likely to experience syncope or cardiac arrest during sleep than those without the ER pattern (hazard ratio, 2.1; 95% confidence interval, 1.2 to 3.5; P=0.008). Additionally, they were able to map the site of origin of ectopic activity in 8 patients and found that the origin of ectopy was consistent with the location of the early repolarization in ECG leads. Haissaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med. 2008;358:

23 In a community-based general population of 10,864 subjects, an ER pattern in the inferior leads was associated with an increased risk of death from cardiac causes. J point elevation of >1 mm in the inferior leads was present in 3.5%, in the lateral leads in 2.4% and in both in 0.1%. J-point elevation of >1 mm in inferior leads was associated with an increased risk of death (adjusted relative risk, 1.28 P = 0.03). J-point elevation >2 mm in inferior leads increased the adjusted relative risk of death from cardiac causes to 2.98 (P<0.001) In a study, ERS was found in 60% of patients with IVF (9 out of 15) versus 3.3% of controls Tikkanen JT, Anttonen O, Junttila MJ, et al. Long-term outcome associated with early repolarization on electrocardiography. N Engl J Med. 2009

24 Type Leads affected Gene mutation VF ER type 1 Lateral leads CACNA1C, CACNB2B Rare ER type 2 Inferior or inferolateral KCNJ8, CACNA1C, CACNB2B Yes ER type 3 Global + Rt precordial leads CACNA1C Yes, electric storms ERS type 4 Brugada syndrome Antzelevitch C, et al. J Wave Syndromes. Heart Rhythm April; 7(4):

25 Possible high risk criteria: Type 3 ERS >2mm ST elevation Syncope FH of SCD Inducible VT/VF? Short coupled PVCs

26 Short coupled PVCs characterizing Brugada and ERS

27 Different epi and endo response to ischemia Epicardium Endocardium LV cavity Gilmour and Zipes, 1980; Yan et al. 2004

28 The concept of phase 2 reentry due to accentuated AP notch during STEMI could answer some questions: Why women with CHD have only a quarter of the risk of SCD as compared to men? (AP notch is more prominent in males). Why VF is more common with RCA occlusion than LAD occlusion? (AP notch is more prominent in RV than LV)

29 Cardiac arrest (VF) Hypoxia Hypothermia Myocardial ischemia Accentuated J wave

30 Since they are sharing common mechanisms, common lines are available for management such as Isoprenaline Increase Ca current and restore AP dome Can terminate electric storms Pacing Eliminate pauses Reduce AP notch Quinidine Inhibits transient outflow K current Resume AP dome ICD For high risk patients

31 Since they are sharing common mechanisms, common lines are available for management such as Future perspectives Selective Ito blockers Selective ATP and AC sensitive K ch blockers for individual cases Gene therapy Epicardial RV pacing??? A proposed management that needs to be studied

32 Epicardial pacing may abolish transmural gradient during AP notch Yan GX, Antzelevitch C. Cellular basis for the electrocardiographic J wave. Circulation. 1996;93:

33 Conclusion J wave syndromes are a group of electric disorders sharing the same mechanisms, characterized by transmural voltage gradient manifested as > 1 mm elevation of the J point + ST elevation featuring BS, ERS, STEMI, and hypothermia. Regional loss of AP dome can precipitate phase 2 reentry and VT/VF. Patients with high risk criteria should receive ICD. Isoprenaline and pacing may stop electric storms. Quinidine is the only available drug that offers benefit.

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35 Increased outward ATP sensitive K + current (IK-ATP ) KCNJ8 gene mutation IK-ATP Haissaguerre M, Chatel S, Sacher F, et al. Ventricular fibrillation with prominent early repolarization associated with a rare variant of KCNJ8/KATP channel. J Cardiovasc Electrophysiol. 2009;20:93 98.