Mechanism of Arrhythmia

Simon Salim
Cardiology Division, Department of Internal Medicine
Cipto Mangunkusumo National General Hospital
Fakultas Kedokteran Universitas Indonesia
Indonesia
 Presenter Disclosure Information
• Simon Salim
– Mechanism of Arrhythmia
– Bradycardia and conduction block

• FINANCIAL DISCLOSURE
– None to declare
Outline

•Arrhythmia
• Epidemiology
• Pathophysiology
• Pathogenesis
•Bradycardia
•Conduction Disruption
Epidemiology

• Arrhythmia Prevalence
• In general:
• Idiopathic incidence 51.9/100,000 (2005-2013): Females 62.0/100,000 vs.
males 42.4/100,000 (p<0.001)1
• In elderly:
• The prevalence of arrhythmia is increasing with age2
• ≥66 yo: persistent (10%) and paroxysmal (5.5%) AF found in 200
outpatient3
• Common types of tachy-arrhythmia in elderly (>60 years old):
• Atrial fibrillation (2x/10 years)2
• Atrial flutter (3x)4
• Ventricular tachycardia (1.3x)1
1. Sirichand et al. Circ Arrhythm Electrophysiol 2017; 10(2): e004662
2. Franken Ra et al. Journal of Geriatric Cardiology : JGC. 2012; 9 :91-100.
3. Lindberg et al., Clinical Interventions in Aging 2016; 11: 1083-1090
4. Juan Granada et al. Journal of the American College of Cardiology. 2000;36.
Pathophysiology – Basic1

Electrical Normal
Impulse Conduction2
Formation2

ARRHYTHMIA3

1. Antzelevitch et Burashnikov. Card Electrophysiol Clin 2011; 3 (1): 23-45

2. Rosen. Am J Cardiol 1988; 61: 2A-8A
3. Hoffman et Cranefield. Am J Med 1964; 37: 670-684
Electrical System and Cardiac Conduction

• Sinoatrial node (SA node)

• Natural pacemaker
• Atrioventricular node (AV node)
• Accepting electrical impulse from SA
node
• Bundle of His
• Connecting electrical system
between atrium and ventricle
• Purkinje fibres
• Spreading electrical impulses to
ventricles
 Na Ca

-90mV

Depolarisasi = aktivasi; Re-polarisasi : kembali ke keadaan istirahat

Pathogenesis of Arrhythmia

Impulse Formation Disruption1

• Automaticity
• Electrolyte: Ca2+ modulation & phosphorylation2
• Parasympathetic ↓ rate3 and Sympathetic ↑ rate4
• Enhanced5:
✓ Negative shift of threshold potential
✓ Positive shift in Maximum Diastolic Potential
✓ ↑ rate phase 4 depolarization

• Triggered Activity
• Overload Ca2+ activating sodium-calcium channel6
• Early or Delayed Depolarization7,8

1. Rosen. Am J Cardiol 1988; 61: 2A-8A

2. Vinogradova et al. Circ Res 2006; 98: 505-514
3. Vanoli et al. Circ Res 1991; 68 (5): 1471-1481
4. Schwartz et al. Circulation 1992. 85 (1 Suppl): 77-91
5. Jalife et al. Basic Cardiac Electrophysiology for the Clinician 2009. 2nd ed; Wiley-Blackwell.
6. Burashnikov et al. Pacing Clin Electrophysiol 2006; 29: 290-295
7. January et al. Eur Heart J 1991; 12: 4-9
8. Cranefield, P.F. Circ Res 1977; 41: 415-423
Pathogenesis - Automaticity

• Increase fibrosis and loss of myocardial fibres in SAN1

• Fibrotic and calcification of cardiac skeleton – start at 30 – 40 years-
old-age
• Cause conduction disturbance : AV block2
• 23 % of 60 years-old have amyloid deposition in atrial3

1. Lev M. Aging changes in the human sinoatrial node. J Gerontol 1954;9:1–8

2. Davies MJ. Pathology of chronic AV Block. Acta Cardiol Suppl 1976;21:19–30.
3. Hodkinson HM, Pomerance A. The clinical significance of senile cardiac amyloidosis: a prospective clinico-pathological
study. Q J Med 1977;46(183):381–387.
4.
Pathogenesis - Automaticity

• Ion flux that can trigger arrhythmia is calcium ions (Ca2+)1

• Aging → reduces activity of Ca2+ handling protein1
• Slowed spontaneous pace-making
• Depressed dynamic response of the heart rate
• Increased incidence of pacemaker problems observed in the elderly
• Enhanced AV Node due to:2
• AMI
• Digitalis ↑
• Isoprenaline
• Cardiac surgery

1. Hatch F, Lancaster MK and Jones SA. Aging Is A Primary Risk Factor For Cardiac Arrhythmias : Disruption of Intracellular
Ca2+ Regulation As A Key Suspect. Expert Review of Cardiovascular Therapy. 2011.
2. De Azevodo et al. Chest 1973; 64: 732-740
PP : Pacemaker Potensial, perlahan –
lahan depolarisasi
MDP : Maximal diastolic potensial,
pada SA : - 70 mV
AP : Action Potensial
TP : Treshold Potensial
Increased Automaticity
Pathogenesis of Arrhythmia

Impulse Formation Disruption1

• Automaticity
• Electrolyte: Ca2+ modulation & phosphorylation2
• Parasympathetic ↓ rate3 and Sympathetic ↑ rate4
• Enhanced5:
✓ Negative shift of threshold potential
✓ Positive shift in Maximum Diastolic Potential
✓ ↑ rate phase 4 depolarization

• Triggered Activity
• Overload Ca2+ activating sodium-calcium channel6
• Early or Delayed Depolarization7,8

1. Rosen. Am J Cardiol 1988; 61: 2A-8A

2. Vinogradova et al. Circ Res 2006; 98: 505-514
3. Vanoli et al. Circ Res 1991; 68 (5): 1471-1481
4. Schwartz et al. Circulation 1992. 85 (1 Suppl): 77-91
5. Jalife et al. Basic Cardiac Electrophysiology for the Clinician 2009. 2nd ed; Wiley-Blackwell.
6. Burashnikov et al. Pacing Clin Electrophysiol 2006; 29: 290-295
7. January et al. Eur Heart J 1991; 12: 4-9
8. Cranefield, P.F. Circ Res 1977; 41: 415-423
Pathogenesis - Triggered Activity

• Early after-depolarization
• Shifts in membrane potential reactivating Ca2+ channels1
• Spontaneous Ca2+ releases from sarcoplasmic2
• Late after-depolarization
• Excessive intracellular Ca2+ or overload3 at resting potential (phase 4)

1. January et al. Circ Res 1989; 64: 977-990

2. Szabo et al. J Cardiovasc Electrophysiol 1994; 5: 933-944
3. Guinamard et al. J Physiol 2004; 558: 75-83
 Early Afterdepolarization

Early Depolarising After Potential (DAP)

Late Afterdepolarization

Late Depolarising After Potential (DAP)

Pathogenesis - Reentry

• Re-Entry
• Conduction Disruption1
• Obstacle
• Anatomical2
• Functional3
• Reflections 4
• Phase 25

1. Rosen. Am J Cardiol 1988; 61: 2A-8A

2. Weiss et al. Circ Res 2000; 87: 1103-1107
3. Allesie et al. Circ Res 1973; 33: 54-62
4. Schmitt et al. Am J physiol 1928; 87: 326-347
5. Di Diego et al. Circulation 1993; 88: 1177-1189
Bradycardia / conduction block

Definition: ≤ 60 bpm1
• Sinus node Dysfunction2
• Atrial origin, AV node / junction origin, His-Purkinje system origin

• Atrio-Ventricular Block2
• Chronic Multi-fascicular Blocks2

1. Glover B & Brugada P (eds). Clinical Handbook of Cardiac Electrophysiology. Springer; 2016
2. Runge, MS, Stouffer, GA, et Patterson, C (eds). Netter’s Cardiology 2nd ed, Saunders Elsevier; 2010
Bradycardia / conduction block

• Sinus node Dysfunction

a. Inappropriate Sinus Bradycardia
b. Sinus Arrest (discharge)
c. Sino-Atrial Exit Block
a. 1st degree
b. 2nd degree (Mobitz I and II)
c. 3rd degree
d. Tachy-Brady Syndrome (sick sinus syndrome)
• Atrio-Ventricular Block
• Chronic Multi-fascicular Blocks

1. Furberg CD, et al. Cardiovascular Health Study Collaborative Research Group. Am J Cardiol 1992;69(16):1329–1335
2. Ostor E et al. Eur Heart J 1981;2(4):317–328.
3. Kannel WB et al. Am J Cardiol 1987;60(17):85I–9
Bradycardia / conduction block
Note: Level of AV Block → supraHIS,
• Sinus node Dysfunction paraHIS, and infraHIS

• Atrio-Ventricular Block
• 1st degree AV Block
• 2nd degree AV Block Mobitz I (Wenckebach)
• 2nd degree AV Block Mobitz II
• 3rd degree AV Block
• Chronic Multi-fascicular Blocks

1. Furberg CD, et al. Cardiovascular Health Study Collaborative Research Group. Am J Cardiol 1992;69(16):1329–1335
2. Ostor E et al. Eur Heart J 1981;2(4):317–328.
3. Kannel WB et al. Am J Cardiol 1987;60(17):85I–9
Electrocardiography

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1. Viljoen et al., Cardiovasc J Afr. 2017; 28(4): 257-260

Bradycardia / Conduction block
Note: Fascicle(s): Right & Left
(Anterior and Posterior) Bundle
branches
• Sinus node Dysfunction
• Atrio-Ventricular Block
• Chronic Multi-fascicular Blocks
• BI-fascicular
1. RBBB + LAFB
2. RBBB + LPFB
3. LBBB (Anterior + Posterior)
• TRI-fascicular
✓ Any of no 1, 2, or 3 + AV Node/HIS Bundle
• Other:
• Alternating RBBB and LBBB
• RBBB + LAFB alternating RBBB + LPFB
1. aa
Abberancies
Take Home Message

• Arrhythmia is equal with geriatric condition

• Think old age ~ think about arrhythmia
• Two main problem in causing arrhythmia :
• Impulse formation & Conduction abnormality
• For bradycardia
• Whatever the cause, unstable hemodynamic → think
pacemaker
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