2. SYNOPSIS
• Anatomy of the Conduction System
• Ion channels and Clinical Implications
• Myocardial Action Potential
• Basis of Arrythmogenesis
• ECG examples of Arrythmias
• Concept of Entrainment
5. SA NODE
• Spindle shaped, 10-20 mm, jxn. Of SVC and
Right Atrium in the sulcus terminalis
• 60% RCA,
• Spindle and spider cells possess pacemaker
characteristics
• Β1, B2, M2 receptors
• Neurotransmitters- Neuropeptide Y, VIP
• Postvagal Tachycardia
7. AV NODE
• Inferior nodal extension,
Compact Portion,
Penetrating bundle
• Koch’s triangle
• AV nodal artery from
crux of RCA (90%)
• Slow propagation
velocity
8. Bundle of HIS
• Continuation of the penetrating bundle of AV
node
• Located in the upper portion of IVS
• Dual blood supply
• Resistant to ishemia
CONDUCTION AV NODE HIS BUNDLE
ATROPINE IMPROVES WORSENS
9. Bundle branches
• Right BB continuation of HIS bundle
• LBB has 2-3 fascicles which are not exactly
bundles, variable anatomy
• LP fascicle resistant to ischemia, dual blood
supply
10. Purkinje Fibres
• Interweaving networks of fibres on the
endocardial surface penetrating 1/3 rd of
endocardium
• Concentrated more at apex and less at base
and papillary muscle tips
• Large surface area and resistant to ischemia
12. Heart Rhythm, Volume 11, Issue 2, Pages 321–
324, February 2014
“ Successful ablation of a narrow complex
tachycardia arising from a left ventricular false
tendon: Mapping and optimizing energy
delivery”
13. Tissues susceptible to ischemia
• SA node
• AV node
• Bundle branches
• HIS bundle, Purkinje fibres resistant to
ischemia
15. Few important concepts on
Nervous distribution
• Sidedness- Right stellate ganglion and vagal nerves
affect the SA node more,
• The left sympathetic and vagal nerves affect the
AV node more
• Tonic vagal stimulation causes greater absolute
reduction in SA rate in presence of tonic
background sympathetic stimulation—
ACCENTUATED ANTAGONISM
• Differential distribution of Sympathetic and
parasympathetic nerves- sympathetic more at
base, PS more in the inferior myocardium
(responsible for vagomimetic effects of Inferior MI)
16. SYNOPSIS
• Anatomy of the Conduction System
• Ion channels and Clinical Implications
• Myocardial Action Potential
• Basis of Arrythmogenesis
• ECG examples of Arrythmias
• Concept of Entrainment
18. Ion Channels
• Named after the Ion like Na,
K, Ca or the NT affecting the
channel like Ik.ach, Ik.atp
• Gating of channels
• Voltage dependence (RMP
of the membrane its
situated on)
• Time dependence
23. Inward Rectifying K+ channels
• I k.ATP ischemic preconditioning, nicorandil
and diazoxide open these channels,
glibenclamide inhibit
• I k.ACH decreases spontaneous
depolarisation in SA node and slows AV
conduction, ADENOSINE increases activity
24. CARDIAC PACEMAKER CHANNEL
• Pacemaker current Funny current “If”
• Encoded by HCN4 gene
• Mutation familial sinus bradycardia
25. CONNEXINS
• Proteins forming the gap junctions which are
responsible for anisotropy in heart
• Connexin 43 abundant in human cardiac
myocardium
MUTATIONS IN:
Carvajal syndrome Desmoplakin
Naxos Disease Plakoglobin
ARVD Plakophilin2
29. SYNOPSIS
• Anatomy of the Conduction System
• Ion channels and Clinical Implications
• Myocardial Action Potential
• Basis of Arrythmogenesis
• ECG examples of Arrythmias
• Concept of Entrainment
31. Heart Rhythm
Volume 11, Issue 7, Pages 1210–19, July 2014
“Synchronization of sinoatrial node pacemaker
cell clocks and its autonomic modulation impart
complexity to heart beating intervals”
32. RESTING MEMBRANE POTENTIAL
• The RMP of a cell is the same as the Nernst
potential of the predominant active ion
channels in the cell
• For Cardiac cells, that which determines the
RMP are the POTASSIUM CHANNELS
• Hence the RMP of a resting cell approximates
– 90 mv (The Nernst potential of K+ channel)
33. Action Potential
• Deviation from RMP as a result of influx and
efflux of ions, leading to increase in positive
charges (Depolarisation) and decrease in
positive charges (Repolarisation)
34. Action potential of the cardiac muscles
• The cardiac action potential is made
of 3 phases:
1. Depolarization:
2. Plateau:
3. Replarization:
35. MAP OF NODE VS MYOCARDIUM
• SA NODE
• AV NODE
• DISEASE MYOCARDIUM
• ATRIAL MUSCLE
• VENTRICULAR MUSCLE
• PURKINJE FIBRE
37. MAP OF MYOCARDIUM
• PHASE 4- THE RMP
• PHASE 0- RAPID UPSTROKE
• PHASE 1- INITIAL DOWNSTROKE
• PHASE 2- PLATEAU
• PHASE 3- FINAL DOWNSTROKE
38.
39. PHASE 4
• 3 MAIN CHANNELS
o Inward rectifying potassium channels-
Potassium efflux helps maintain negativity
o Na-Ca exchanger
o Na-K ATPase
40. PHASE 0
• 2 inward currents
• SUDDEN INCREASE IN MEMBRANE INFLUX OF
Na+
• Stimulus should be enough to take the MP
past the threshold, beyond which “the size of
AP is independent of the strength of the
stimulus- ALL OR NONE RESPONSE”
• Later part of upstroke is contributed by Slow
Inward Ca channel opening
41. • Initial curve- FAST RESPONSE Na channels
Time dependent inactivation, usually close at
around + 60 mv
• Later curve- SLOW RESPONSE L-Ca channels
Activated at around -30 mv, continue into the
plateau phase
Class 1A inhibit
Class IV inhibit
42. Phase 1-Early rapid repolarisation
• Inactivation of inward Na current
• Activation of 3 main outward currents leading
to efflux of positive charges
o K+
o Cl-
o Na/Ca exchanger
• Typical notch
44. Phase 2-Plateau phase
• Competition between the outward and inward
currents lead to Plateau phase
• Steady state phase
45. Phase 3-Final rapid repolarisation
• Time dependent inactivation of Inward L-Ca
current
• Activation of a number of K+ channels-Ikr, Iks,
Ik.ach, Ik.ca-leading to outward K+ current and
loss of positivity return to a more negative
steady state (the RMP)
46.
47. K+ channels-Ikr, Iks, Ik.ach, Ik.ca
Prolongation of plateau phase
Prolongation of action potential
LONG QT
HERG
mutation
Erythromycin
Ketoconazole
48. MAP OF SA & AV NODE
• PHASE 4- SLOW DIASTOLIC DEPOLARISATION
“PACEMAKER POTENTIAL”
• PHASE 0- SLOW UPSTROKE
• PHASE 3- DOWNSTROKE
49.
50. PHASE 4 “PACEMAKER POTENTIAL”
• SLOW DIASTOLIC DEPOLARISATION- “no REST
for SA node, AV node”
• Maintained by Funny currents “If”
• Hyperpolarisation current activated by Na and
K+, Transient Ca2+ channels
• Influenced by adrenergic and cholinergic
neurotransmitters
56. POST REPOLARISATION REFRACTORINESS
• Even after the restoration
of RMP in a cell, it
continues to remain in a
state of refractoriness to
stimuli and hence non
excitable
• This period is called
POST REPOLARISATION
REFRACTORINESS, which is
a time dependent
phenomenon
57. Classification of Antiarrhythmic Drugs
based on Drug Action
CLASS ACTION DRUGS
I. Sodium Channel Blockers
1A. Moderate phase 0 depression and
slowed conduction (2+); prolong
repolarization
Quinidine,
Procainamide,
Disopyramide
1B. Minimal phase 0 depression and slow
conduction (0-1+); shorten
repolarization
Lidocaine
1C. Marked phase 0 depression and slow
conduction (4+); little effect on
repolarization
Flecainide
II. Beta-Adrenergic Blockers Propranolol, esmolol
III. K+ Channel Blockers
(prolong repolarization)
Amiodarone, Sotalol,
Ibutilide
IV. Calcium Channel Blockade Verapamil, Diltiazem
59. Heart Rhythm
Volume 11, Issue 3, Page e1, March 2014
“Propranolol, a β-adrenoreceptor blocker, prevents
arrhythmias also by its sodium channel blocking effect”
60. SYNOPSIS
• Anatomy of the Conduction System
• Ion channels and Clinical Implications
• Myocardial Action Potential
• Basis of Arrythmogenesis
• ECG examples of Arrythmias
• Concept of Entrainment
65. ROLE OF ANS
• Alterations in vagal and sympathetic
innervation and sensitivites to the same,
can lead to heterogeneity within the
myocardium and hence serve a substrate to
various arrthymias
• AUTONOMIC REMODELLING
66. ROLE OF ANS
• Alterations in vagal and sympathetic
innervation and sensitivites to the same,
can lead to heterogeneity within the
myocardium and hence serve a substrate to
various arrthymias
• AUTONOMIC REMODELLING
72. AUTOMATICITY
• Property of a fibre to initiate an impulse
spontaneously, without need for an initial
stimulation
73. Normal Automaticity
• Normal pacemaker mechanism behaving
inappropriately
Eg:
1.Persistent sinus tachycardia at rest
2.Sinus Bradycardia during exercise
74. Abnormal Automaticity
• Escape of a latent pacemaker
• Due to abnormal ionic mechanisms, other
pacemaker sites gain predominance over SA
node
• Secondary to spontaneous submembrane Ca
elevations, abnormal electric and ionic mileu
leading to spontaneous depolarisation
(Eg-Myocardial infarction)
77. PARASYSTOLE
• Fixed rate asynchronously discharging
pacemaker
• Not altered by the dominant rhythm (Entrance
Block)
• Inter discharge interval is multiple of a basic
interval
• May be Phasic or Modulated
80. TRIGGERED ACTIVITY
• Initiated by AFTER DEPOLARISATIONS
o EARLY AFTER DEPOLARISATION
o DELAYED AFTER DEPOLARISATION
Not all after depolarisations reach the threshold
potential (all or none response), but if they do,
they would self perpetuate
81. EARLY AFTER DEPOLARISATION
• TYPE 1 -occurs during PHASE 2 of MAP
• TYPE 2 –occurs during PHASE 3 of MAP
• Substrate-
- prolonged plateau phase (action potential duration)
- leads to excess intracellular calcium,
-invokes a series of pumps (the Na+ pump), causing
depolarisation
82.
83. Egs of EAD
• LONG QT SYNDROME AND ASSOCIATED
VENTRICULAR TACHYCARDIAS (inc. TdP)
- GENETIC CAUSES
- ACQUIRED CAUSES (class Ia and III
antiarrythmics, Macrolide antibiotics)
• Magnesium and Potassium channel openers
like Nicorandil suppress these EADs
87. DELAYED AFTER DEPOLARISATION
• Occur after completion of Phase 4 of MAP
• Activation of calcium sensitive inward current
Eg:
• Mutations in RYR2 gene encoding
Calsequestrinincreased sensitivity of RyR2
channel to catecholaminesDADCPVT
ABNORMAL CALCIUM HANDLING
88.
89. Proposed scheme of events leading to
delayed after depolarizations and triggered tachyarrhythmia
90. CPVT
DAD-mediated CPVT. Mutations in the ryanodine receptor (RyR) result in leakage of Ca2+
from sarcoplasmic reticulum (SR) into cytoplasm.
92. DISORDERS OF IMPULSE CONDUCTION
• Blocks
- tissue blocks, rate dependent blocks
- responsible for some of the bradyarrythmias
• Reentry
- heterogeneity in tissues
- responsible for most of the tachyarrythmias
93. Blocks
• Tissue becomes “inexcitable” and when there
is no escape to the propagating impulse, it
manifests as bradyarrythmias
• Can occur at any level of the conduction
system
• Anatomic reasons (fibrosis-degenerative or as
a consequence to the pathological process)
• Functional reasons (Rate dependent blocks)
94.
95. Rate dependent blocks
• Deceleration dependent blocks
-Reduced ‘spontaneous diastolic depolarisation’ at
slow rates is the cause
-? Role of digitalis
• Tachycardia dependent blocks
-post repolarisation refractoriness (incomplete recovery of
excitabilty when the next impulse arrives) of 1 or the other
bundle branches, is the cause
98. DISORDERS OF IMPULSE CONDUCTION
• Blocks
- tissue blocks, rate dependent blocks
- responsible for some of the bradyarrythmias
• Reentry
- heterogeneity in tissues
- responsible for most of the tachyarrythmias
99. REENTRY
• Heterogeneity in spread of depolaristion
within a tissue is the cause
• Slow and Fast pathways
• Repeated Impulse reentry into the conduction
system through an excitable pathway leads to
sustaining of the tachycardia
reentrant tachycardia/ reciprocating
tachy/circus movement/ echo beat
101. Types of Reentry
• Anatomical reentry
- 2 distinct heterogeneous pathways of
conduction, each with differrent
electrophysiological properties, creating a slow
and a fast pathway
- can occur at level of SA node, Atrium, AV node,
Ventricle, Accessory pathways (WPW pattern)
• Functional reentry
-dispersion of excitability, refractoriness or both
within a tissue
-Egs: Post Infarction, failing heart
105. Atrial Flutter
-TYPICAL FLUTTER,
counterclockwise moving
from caudocranial
direction in the interatrial
septum
-recurrence can occur in
cases of other pathways of
reeentry, specially seen in
cases like ASD with
AFlutter
107. Atrial Fibrillation
-micro entry circuits due
to spatio-temporal
disorganisation within
the atrium
-MULTIPLE WAVELET
HYPOTHESIS
-anatomic remodelling
-electric remodelling of
the atrium
-Role of Micro RNAs
-Ion channel
abnormalities
-Familial AF (KCNQ1)
108.
109. Heart Rhythm Volume 11, Issue 7,
Pages 1229–1232, July 2014
Marshall bundle reentry: A novel type of
macroreentrant atrial tachycardia
110. AV NODAL REENTRY
-Sudden onset and
termination
-Variation in cycle length
“exposes” the AV nodal
heterogeneity and stats
the reentry
•SLOW-FAST pathway
(Typical)
•FAST-SLOW pathway
•SLOW-SLOW pathway
111. AV REENTRY
Location of accessory pathways
-Accessory bundles of
conducting tissue
“Preexcitation”impulses
conducted to ventricles
thru’ these pathways
earlier than the usual
oneWPW PATTERN
117. BRUGADA
SYNDROME
BRUGADA PATTERN
-Phase 2 reentry
-Mutations in genes
encoding Na
+ channels (SCN5A gene)-
>alterations in Na channel
currentheterogeneity in
AP in RV epicardium
-ICDs are the only proven
therapies to avert SCD in
such pts.
118. • Importance of using PROPER ECG ELECTRODE
POSITIONS and HIGH PASS FILTERS (0.05-0.35 HZ)
during a recording of ECG
122. “Rotor Stability Separates Sustained
Ventricular Fibrillation From Self-Terminating
Episodes in Humans”
J Am Coll Cardiol. 2014;63(24):2712-
2721. doi:10.1016/j.jacc.2014.03.037
123. SYNOPSIS
• Anatomy of the Conduction System
• Ion channels and Clinical Implications
• Myocardial Action Potential
• Basis of Arrythmogenesis
• ECG examples of Arrythmias
• Concept of Entrainment
124. OVERDRIVE PACING
• After cessation of pacing,
- It can increase the amplitude and shorten the
cycle length of the complexes (overdrive
acceleration) suggest the mechanism of
arrythmia is DELAYED AFTER DEPOLARISATION
- It can terminate the underlying
tachycardiasuggest the underlying
mechanism of arrythmia is REENTRY
125.
126. ENTRAINMENT
• “En-training” the tachycardia simply means
increasing the rate of tachycardia by pacing
• Resetting of the reentrant circuit with the pacing
induced activation
• Resumption of the intrinsic rate of the
tachycardia when the pacing is stopped
• Implications:
-used to prove the reentrant mechanism of the
tachycardia,
-used to locate the reentrant pathway
127.
128. SUMMARY
• ANATOMY OF CONDUCTION SYSTEM
• IMPORTANT ION CHANNELS AND THEIR
CLINICAL IMPORTANCE
• MYOCARDIAL ACTION POTENTIAL
• MECHANISMS OF ARRYTHMOGENESIS
• FEW CONCEPTS-
Overdrive Pacing, Entrainment,
Drugs Causing And Treating Arrythmias
129. CONCLUSION
“An attempt should be made to study the
basis of each arryhthmia we come across, in
order to terminate it with appropriate
pharmacological/ intervention and also
prevent its recurrence”
130. REFERENCES
• BRAUNWALD TEXTBOOK
• HURST TEXTBOOK
• ZIPES’ ELECTROPHYSIOLOGY
• LITERATURE SEARCH OF 2013-2014 ISSUES
“HEART RHYTHM”, “JACC”
After cesssation of vagal stimulation, the sinus node rate accelrates transiently
GENETIC BASIS OF CARDIAC ARRYTHMIAS
Abnormalities in these….Central to many arryhtmias as we would see later…
We ld see abt them when we study MAP….
How does the sa node know that it should be beating every n th second….
-ATRIAL AND VENTRICULAR MUSCLE-SA AND AV NODE AND DISEASED MYOCARDIUM
DIAGRAM OF BOTH
Very broad concept….
Animal models
Animal models
After a disease process likde MI, Heart failure….
Each will be explained with examples of ECGs…by the end of it, we will be able to trace the underlying mechanism of many of the common arryhtmias we see in clinical practice….understanding the mechanism helps in treating them whetehr pharmacologically or with procedures like RFA…
Biological clock starts behaving inappropriately…
The dominant rhythm modulates the parasystole to slow down or speed up its rate…
Background
Bradycardia dep. Block…Paradoxical situtaion…mechanisms are not known and controversial but fr now….
AS MENTIONED EARLIER, CAN OCCUR AT ANY LEVEL….
MAGNESIUM, VERAPMAIL
Verapamil sensitive….benhassen vt s….
The rotor hypothesis states that VF is maintained by a single intra mural Mother rotor (reentry circuit), which develops blocks and breaks into daughter wavelets causing fibirllation….
Before going into egs of each of these reentrant tachycardias, we will discuss this important concept of entrainment….
IN THE COURSE OF THE PRESENTATION WE VE GINE THRU THE…….