1. ECG Workshop in Cardiac Ion Channel Diseases Dr. Ngai-Shing Mok Dept of Medicine & Geriatrics Princess Margaret Hospital Hong Kong

2. M/31 Good past health Found dead on bed in the morning Hx of syncope without warning while walking 2 weeks before his death No family hx of sudden death Autopsy – no structural heart disease Toxicology screening -ve Case One

3. Baseline ECG before Treadmill Exercise Test

4. ECG during Treadmill Exercise Test

5. Questions (1)What are the ECG abnormalities ? (2)How are you going to confirm the diagnosis ?

6. Baseline ECG before Treadmill Exercise Test

7. ECG during Treadmill Exercise Test

8. Mean age : 32 yrs M:F - 9:2 N = 289 BMI - 24.6

9. Baseline ECG – normal During exercise test – 2mm coved-type ST elevation in V1 only Baseline ECGECG during exercise test Brugada syndrome ???

10. ECG of his parent showing complete RBBB but no Brugada ECG pattern Family ECG screening

11. 1st molecular autopsy in PMH

12. P1956_P1959del Molecular autopsy found a heterozygous 12- nucleotide deletion in CACNA1C

13. Cardiac LTCC plays a pivotal role to regulate heart rhythm and contractility Mutations in LTCC reported to be associated with inherited arrhythmogenic diseases Brugada syndrome (BrS) Long & short QT syndrome (LQTS, SQTS) Idiopathic VF (IVF) Early repolarization syndrome (ERS) Cardiac L-type calcium channel (LTCC)

14. Learning Points

15. M/40 Good past health 3 younger brothers died of sudden nocturnal death at age 30+ years with –ve autopsy Referred for family screening All along no hx of syncope Case Two

16. Baseline ECG at rest

17. (1)What are the ECG abnormalities ? (2)What are the DDx ? (3)What further test would you like to perform to confirm your Dx ? Questions

18. Baseline ECG at rest

19. Type 2 Brugada ECG ?

20. Corrado Index (STJ/ST80 >1) c/w Type 2 Brugada ECG

21. 6mm The base of the triangle 5mm below high take off > 3.5mm Favours type 2 Brugada ECG

22. β >58 degrees β >58 degrees favours type 2 Brugada ECG & predicts a positive drug provocation test to unmask Type 1 Brugada ECG

23. ECG after IV flecainide provocation test V1 & V2 on 4 th ICS Flecainide provocation test

24. V1 & V2 recorded on 3 rd ICS after IV flecainide provocation

25. Pre-flecainide Post-flecainide Flecainide provocation test converted type 2 to type 1 Brugada ECG

26. Controversy in the prognostic value of EP Study in BrS

27. PRELUDE Study PRogrammed ElectricaL stimUlation PreDictivE value in BrS A large prospective study to determine the role of EPS in risk stratification in BrS Priori et al. JACC 2012 Inducible VT/VF does not predict high risk in BrS

28. Priori et al. Circulation 2002 Risk factors and prognosis of BrS

30. (1)ICD implanted despite –ve EP study in view of very strong FHx of SD (considered as risk predictor in Japanese guidelines) (2)Genetic study found mutation in his CACNAIC gene ? pathogenicity

31. Learning Points

32. F/14 Good past health Suddenly collapsed with LOC after chasing and boarding a bus Hx of syncope 9 months ago after she quarrelled with her friend No family hx of sudden death Case Three

33. ECG recorded by AED

34. NS Mok ECG recorded in sinus rhythm after successful defibrillation

35. NS Mok Wide-complex tachycardia recorded in ICU

36. NS Mok Signal-averaged ECG : no late potential Echo : no structural heart disease CT brain : evidence of hypoxic brain damage Coronary MRA : no anomalous origin of coronary arteries Viral study for myocarditis : negative Investigations

37. Questions (1)What are the ECG features during sinus rhythm ? (2)What is the tachycardia recorded in ICU ? (3)What are the DDx of such tachycardia ? (4)How would you confirm the Dx ?

38. NS Mok ECG recorded in sinus rhythm after successful defibrillation

39. NS Mok Wide-complex tachycardia recorded in ICU

40. NS Mok VT with beat-to-beat alteration of QRS axis Bi-directional VT

41. NS Mok 1.Advanced heart disease 2.Digitalis intoxication 3.Aconite poisoning due to overdose of “ 川烏、 草烏 ” 4.Familial hypokalaemic periodic paralysis 5.ARVD Type 2 6.Catecholaminergic polymorphic VT (CPVT) DDx of bi-directional VT

42. Polymorphic VT Bi-directional VT Monomorphic PVCs Mok NS et al CMJ 2006 CPVT confirmed by hRyR2 mutation Adrenaline provocation test

43. SCD / NS Mok CPVT should be suspected in young patients without structural heart disease presenting with syncope /sudden cardiac arrest / polymorphic VT / bi- directional VT induced by exercise or emotion Absence of structural heart disease Manifests in childhood and adolescence with a high lethality rate (30 – 50% mortality by age 30) Stress test (exercise or adrenaline infusion) and/or genetic test should be done if CPVT a DDx β-blockers is the cornerstone of therapy and will improve prognosis of patients Catecholaminergic Polymorphic VT (CPVT)

44. Bi-directional VT with a RBBB pattern & alternating QRS axis Catecholaminergic Polymorphic VT (CPVT)

45. SCD / NS Mok VFVTVT VT Exercise test induced bi-drectional VT in CPVT FF, Female; 17yrs; Exercise test

46. NS Mok P.G, female, 9yrs Catecholaminergic bi-directional VT degenerating into VF

47. Learning Points

48. Case Four F/55 Hx of DM, IHD s/p PCI to RCA done Sudden collapse with LOC while shopping in Shenzhen Spontaneous recovery Visited PMH AED in the same afternoon

49. NS Mok ECG recorded in AED during a witnessed convulsion

50. (1)What are the ECG abnormalities ? (2)What is the single most important question you should ask the patient ? (3)What is the underlying cause ? (4)How would you treat this patient ? Questions

51. NS Mok ECG recorded in AED during a witnessed convulsion

52. NS Mok SSL Torsades de pointes QTc 600ms S-L-S sequence initiated Torsades de Pointes resulting in syncope

53. NS Mok Progress (1) TdP suppressed by IV magnesium sulphate & transvenous temporary pacing at 100 beats/min

54. NS Mok Normalization of QTc 4 days after withdrawal of ketoconazole Progress (2)

55. NS Mok Drugs associated with LQTS www.torsades.org K+ Na+ Antiarrhythmic Drugs Quinidine, Procainamide Disopyramide Sotalol, Amiodarone Sotalol, AmiodaroneAntibiotics Erythromycin, Trimethoprim & Sulfamethaxazole, Pentamidine, Clarithromycin, Azithromycin Antihistamines Terfenadine, Astemizole, diphenhydramine Antifungal Fluconazole, Ketoconazole Antimalarial Chloroquine, Halofantrine Antipsychotic Drugs Haloperidol, Tricyclic antidepressants

56. NS Mok 1.Avoid QT-prolonging drugs in patients at risk of TdP 2.Avoid >1 QT-prolonging drug at the same time 3.Avoid combination of QT-prolonging drug & cytochrome P450 inhibitor 4.Cardiac & QTc monitoring in the first few days when giving QT-prolonging anti-arrhythmic drugs to at-risk patients 5.Avoid hypokalaemia in patients receiving QT-interval prolonging drugs Good Practice to Avoid Drug-induced TdP

57. Learning Points

58. Case Five M/12 History of syncope while running Younger sister died of drowning at age of 10 LQTS suspected and Treadmill exercise test was done

59. Resting ECG prior to exercise stress testing

60. ECG during exercise stress testing

61. (1) What are the ECG findings at rest and during exercise ? (2) What is his Schwartz score ? (3) Does he suffer from Long QT syndrome ? Questions

62. Resting ECG prior to exercise stress testing

63. ECG during exercise stress testing

64. Resting ECG prior to exercise stress testing QT = 470ms RR = 1.16s QTc = 440ms

65. Resting ECG prior to exercise stress testing QT = 470ms RR = 1.16s QTc = 440ms

66. NS Mok Diagnostic criteria of LQTS ≤ 1 point – low probability >1-3 points – intermediate probability ≥ 3.5 points – high probability of LQTS (revised 2006) Schwartz PJ 1993 Schwartz Schwartz Score Total Schwartz score = 2.5

67. ECG during exercise stress testing QT = 340ms RR = 0.52s QTc = 470ms QTc prolonged by ≥ 30ms Suggesting LQT1 syndrome

68. Learning Points

69. Thank You ! Princess Margaret Hospital Hong Kong