arrhythmia pathology and treatment in brief

1. Treatment of various arrhythmias
Presenter –
Dr Chimi Handique
PGT
Dept of Pharmacology

2. What is arrhythmia ?
• a – “without” rhuthmos – “ryhtm” i.e it means “without
rhythm”.
• Also known as “ cardiac dysrhythmia”
• Cardiac arrhythmias are a group of conditions in which the
heart beats with an irregular or abnormal rhythm.

3. Normal cardiac electrophysiology

4. Properties of cardiac cells
• Excitability –
It is the ability of cardiac cells to respond to a suitable
amount of stimuli and produce an electric potential, also
called electrical impulse.
• Conductivity –
It is the ability of cardiac cells to transfer the action potential
generated at the sino-atrial node from cell to cell.

5. •Contractility –
It is a cardiac muscle cell’s ability to transform an electrical
signal originating at sino-atrial node into mechanical action
•Rhythmicity –
It is the property of cardiac muscle cells which describes their
ability to contract regularly without the involvement of any
nerves.

6. Normal cardiac rhythm
Heart rate should be between 60 and 100 per minute.
All the cardiac impulses should originate from the SA
node of the heart.
The impulse should conduct through the normal
conduction pathway.
The impulse should pass through conducting pathways
with normal velocity.

7. The impulse begins at the SA node and the electrical activity
spreads through the walls of the atria and causes them to contract
The AV node located between
the atria and the ventricles
acts like a gate that slows that
signal before it enters the
ventricles. This delay gives the
atria time to contract before
the ventricles
His purkinje network – this pathway of fibres sends the impulses to
the muscular walls of the ventricles and causes them to contract

8. Phase 0
Phase 4
Phase 3
Phase 2
Phase 1
- 90 mV
0 mV
30 mV
Cardiac action potential of non nodal tissue

9. -100
-80
-60
-40
-20
0
20
Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
Na+
ca++
ATPase
mv Cardiac Action
Potential
Resting membrane
Potential
Na+
m
Na+
Na+
Na+Na+
Na+
h
K+
ca++
K+
K+K+
ca++ca++
(Plateau Phase)
K+K+K+ Na+
K+
Depolarization

10. -100
-80
-60
-40
-20
0
20
Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
Na+
ca++
ATPase
mv Cardiac Action
Potential
R.M.P
Na+
m
Na+
Na+
Na+Na+
Na+
h
K+
ca++
K+
K+K+
ca++ca++
(Plateau Phase)
K+K+K+ Na+
K+
Depolarization
Phase 4
(only in pacemaker
cells

11. Differences between non pacemaker and
pacemaker cell action potentials

12. Arrhythmia pathogenesis
 Disorder of impulse formation.
 Automaticity.
 Triggered Activity.
- Early after depolarization.
- Delayed after depolarization.
 Disorder of impulse conduction.
 Impulse Block
 Re – entry phenomena

13. Abnormal impulse generation

14. Abnormal automaticity
• The SA node is the heart’s natural pacemaker
Any impulses fired from elsewhere in the heart before or
concurrently with SA node firing can lead to premature
heartbeats or sustained abnormal heartbeats.
• Problems associated are
– sinus tachyarrhythmia
– sinus bradyarrhythmia
– Abnormality in site of impulse generation ,ectopic loci
– Escape rhythms

15. Triggered automaticity
• This is an abnormal secondary upstroke which occur only after
a normal initial or “triggering “ upstroke or action potential.
• These secondary upstrokes are called after --depolarization's
• This may be of two types
– Early after depolarization
– Delayed after depolarization

16. Early after depolarization
Torsa de pointes
 Hypokalemia
 low heart rates

17. Delayed after depolarizations
Adrenergic stress
Digitalis intoxication
Ischemia

18. Abnormal impulse conduction

19. Conduction block
• Conduction block may occur due to depression of impulse
conduction at AV node & bundle of His, due to vagal
influence or ischaemia .
• Types :
1st degree heart block – slowed conduction
2nd degree block – some supraventricular complex not
conducted
3rd degree block – no supraventricular complex are
conducted

20. Re entry phenomena
• It can be of two types
• Anatomically defined re entry
– Classic example – wpw syndrome
• Functionally defined reentry
– Mostly seen in patients with ischemic heart disease

22. Reentry Arrhythmias

23. Types of
arrhythmiaPremature beats
Supra ventricular
arrhythmias
Ventricular
arrhythmia
AV Blocks
Bradyarrhythmia
Atrial Tachycardia
PSVT
Atrial Fibrillation
Atrial Flutter
•Ventricular
Tachycardia
•Torsade pointes
•Ventricular Fibrillation

24. ARRHYTHM
IAS
ACUTE THERAPY CHRONIC THERAPY
FIRST CHOICE ALTERNATIVES FIRST CHOICE ALTERNATIVES
1 AF/AFL DCC VERAPAMIL
DILTIAZEM
Β BLOCKER
DIGOXIN Β BLOCKER
CCB
2 PSVT DCC
ADENOSINE
Β BLOCKER
CCB
ICD AMIODARONE
Β BLOCKER
3 VT LIDOCAINE
CARDIOVERSION
PROCAINAMIDE
MEXILETINE
AMIODARONE
AMIODARONE
DOFETILIDE
MEXILETINE
PROPRANOLOL
PROPAFENONE
4 TORSADES DE
POINT
DCC
PACING
ISOPRENALINE
MAGNESIUM
5 VF ELECTRICAL
DEFIBRILLATION
LIDOCAINE
AMIODARONE
ICD AMIODARONE
Β BLOCKER
6 WPW CARDIOVERSION AMIODARONE
PROPAFENONE
PROCAINAMIDE
AMIODARONE
PROPRANOLOL
QUINIDINE
PROPAFENONE

25. Management of arrhythmias
• Pharmacological therapy.
• Cardio version.
• Pacemaker therapy.
• Surgical therapy
• Interventional therapy

26. Anti arrhythmic drugs
Vaugham-Williams classification
This classification was introduced in 1970
CLASS MECHANISM
I Na+ channel blocker
II Beta blocker
III K+ channel blocker
IV Calcium channel blocker

27. • In addition
• For PSVT - adenosine, digoxin
• For AV Block –
– sympathomimetics – isoprenaline
– Anticholinergics – Atropine
• Digitalis is used in AF, AFL AND PSVT to control
ventricular rate

28. Mechanisms of anti arrhythmic drugs
• To suppress automaticity
– ↓ Rate of phase 0
– ↓ Slope of phase 0
– Duration ERP ↑
– TP less negative
– Resting membrane potential more negative
• For EAD’s
– IV isoproterenol
– Pacemaker
– magnesium

29. • DAD’s
– To prevent loading of Ca+ and Na+ loading in the cell
• Abolishing reentry
– Slow conduction
– ↑ ERP

30. Class I – Na+ channel blockers
• The primary action of these class of drugs is
– To limit the conductance of Na+ across the cell
membrane
– Reduce the rate of phase 4 depolarization
• They are further divide into three subclasses
– Subclass IA
– Subclass IB
– Subclass IC

31. Na+ channel blockers – subclass IA
• The anti arrhythmic drugs include
– quinidine
– procainamide.
• They are open state Na+ channel blockers.
• This class of drugs moderately delay the channel recovery.
• They suppress the AV conduction and prolong refractoriness

32. • Lengthen action potential
• Slow rate of rise of phase 0
• Prolong repolarization
Subclass IA
QUINIDIINE
PROCAINAMIDE
DISOPYRAMIDE

33. Na+ channel blocker – subclass IB
• They block the Na+ channels more in inactivated than in open
state, but do not delay channel recovery.
• They have little or no effect at slower heart rates, and more
effects at faster heart rates
• They either do not change the action potential duration, or they
may decrease the action potential duration.
• Class IB drugs tend to be more specific for voltage gated Na
channels than Ia.

34. Subclass IB
LIDOCAINE
MEXILITINE
•Limited effect on rate of rise of
phase 0
•Shorten repolarization
•Shorten QT interval
•Shorten the action potential

35. Na+ channel blockers – subclass IC
• Most prominent action is on open state Na+ channels and
have the longest recovery time
• Thy delay conduction and prolong the P-R interval, broaden
the QRS complex
• They have minimal effect on action potential duration
• This class of drug has high proarrhythmic potential

36. Subclass IC
PROPAFENONE
FLECAINIDE
•No effect on length of action
potential
•Markedly reduces rate of
rise of phase 0
•Markedly prolongs PR and
QRS

37. Class II – adrenergic agents
• Class II agents are conventional beta blockers
• They act by blocking the effects of catecholamines at the β1-
adrenergic receptors, thereby decreasing sympathetic activity
on the heart.
• They decrease conduction through the AV node.
• They prolong PR interval, but no effects on QRS or QT
interval

38. •Propanolol
•Metoprolol
•Esmolol

40. Class III – K+ channel blockers
• Class III agents acts by prolonging repolarization.
• These agents do not affect the sodium channel, so conduction
velocity is not decreased.
• The prolongation of the action potential duration and
refractory period, combined with the maintenance of normal
conduction velocity, prevent re-entrant arrhythmias.
• Class III agents have the potential to prolong the QT interval of
the ECG.

41. Amiodarone
Dronedarone
Dofetilide
ibutilide

42. Newer class III
Dronedarone
Tedisamil
Vernakalant
Azimilide
Without iodine, short t1/2, AF
Oral 400mg twice daily
Na+ & K+, atrial ERP increased, AF
Block both rapid & slow k+ channel

43. Class IV- calcium channel blockers
• The primary action of this class of drug is to inhibit Ca2+
mediated slow inward current.
• They decrease conduction through the AV node, and shorten
phase two (the plateau) of the cardiac action potential.
• They thus reduce the contractility of the heart, so may be
inappropriate in heart failure.
• They slow sinus rhythm, prolong PR interval, no effect on
QRS complex

44. DRUGS USED ARE
VERAPAMIL AND DILTIAZEM

45. Phase 0
Phase 1
Phase 2
Phase 3
Phase 4
R.M.P
(Plateau Phase)
Class I:
Na + channel blockers.
- Pacemaker potential
-
-
-
Class III:
K + channel blockers
-
Class IV:
Ca ++ channel blockers
Class II:
Beta blockers

46. Treatment of various
arrhythmias

47. Premature beats
• Premature beats are the most common type of arrhythmia.
• Premature beats that occur in the atria are called premature
atrial contractions, or PACs and those that occur in the
ventricles are called premature ventricular contractions
• PACs are common and may occur as the result of stimulants
such as coffee, tea, alcohol, cigarettes, or medications.
• Treatment is rarely necessary

49. Sinus tachycardia
• Sinus tachycardia is a heart rhythm originating from the SA
node with an elevated rate of impulses, defined as a rate greater
than 100 beats/min in an average adult.
• Sinus tachycardia is usually a response to normal physiological
situations, such as exercise and an increased sympathetic tone
with increased catecholamine release—stress, fright, flight,
anger
• Treatment not required for physiologic sinus tachycardia.
Underlying causes are treated if present.

51. Paroxysomal supraventricular
tachycardia
• Here the heart rate ranges from 160 – 250 beats per min
• There are 2 common types
– Atrio ventricular reciprocating tachycardia
– AV nodal reentrant tachycardia
– Wolf Parkinson white syndrome

52. AV nodal Re entrant Tachycardia
• AVNRT develops because of the presence of two electro
physiologically distinct pathways for conduction in the complex
the AV node.
• The fast pathway in the more superior part of the node has a
longer refractory period, whereas the pathway lower in the AV
node region conducts more slowly but has a shorter refractory
period.
• As a result of the inhomogeneities of conduction and
refractoriness, a reentrant circuit can develop in response to
premature stimulation.

53. AV Nodal Reciprocating Tachycardia
• Patients with AVRT have been born with an extra, abnormal
electrical connection in the heart.
• In AVRT, the extra connection, which is often called
an accessory pathway, joins one of the atria with one of the
ventricles
• In some patients with AVRT, the accessory pathway is
capable of conducting electrical impulses in both directions
while in other patients the accessory pathway can only
conduct electrical impulses in one direction or the other.
.

54. • This difference turns out to be important. In most patients
with AVRT, the impulses can only go across the accessory
pathway from the ventricle to the atrium.
• Patients in whom the impulses can travel across the
accessory pathway in the other direction - from the atrium to
the ventricle - are said to have Wolff-Parkinson-White
(WPW) syndrome

55. Management of PSVT
Acute Management
• Patients with haemodynamic instability require emergency
cardioversion.
• If the patient is haemodynamically stable, vagal manoeuvres,
can be successfully employed.
• If not successful, the administration of adenosine, 6–12 mg
IV, frequently does so.
• Intravenous beta blockade or calcium channel therapy
should be considered as second-line treatment.

56. Long-term management
• It includes ablation of the accessory pathway.
• Also, verapamil, diltiazem & β-blockers are effective in 60-
80% of patients.

57. Adenosine
• Endogenously produced important chemical mediator used
in PSVT
• MOA:
– Activation of Ach sensitive K+ channel - membrane
hyper polarization of SA node (G-protein coupled
adenosine receptor) – depression of SA node and also
slowing of AV conduction and shortening of action
potential in atrium
– Also indirectly reduces CA++ current in AV node –
depression of reentry in PSVT

58. • Very short half life – 20-30 sec. - Uptake by RBCs and
endothelial cells
• Administered intravenously
– 6 mg given as a rapid intravenous bolus (administered
over a 1-2 second period)
– If the first dose does not result in elimination of the supra
ventricular tachycardia within 1-2 minutes, 12 mg should
be given as a rapid intravenous bolus
• ADR: chest tightness, dyspnoea, fall in BP and flushing etc.

59. Wolf Parkinson White Syndrome
• An abnormal band of atrial tissue connects the atria and the
ventricles and can electrically bypass the normal conducting
pathways
• A reentry circuit develops causing paroxysms of tachycardia.
• Drug treatment includes flecainamide, amiodarone or
disopyramide
• Digoxin and verapamil are contraindicated
• Transvenous catheter radiofrequency ablation is the
treatment of choice

61. Flecainide
 Proarrhythmogenic
effect on patients with
coronary artery disease
 Used in refractory
ventricular arrhythmia
 A/E – torsades de point,
visual disturbances &
headache
Disopyramide
Anticholinergic &
depressant - SAN
A/E - Myocardial
deprssion, urinary
retention
C/I BHP& CHF

62. Atrial Flutter
• HR ranges between 200-350/min
• Here the electrical signals come from the atria at a fast but
even rate, often causing the ventricles to contract faster and
increase the heart rate.
• When the signals from the atria are coming at a faster rate
than the ventricles can respond to, the ECG pattern develops
a signature "sawtooth" pattern, showing two or more flutter
waves between each QRS complex.

64. Treatment
• For acute paroxysm – Cardio version
– It requires a lower energy shock. 20-50J is commonly
enough to revert to sinus rhythm
• Recurrent paroxysms may be prevented by class Ic and class
III agents
• The treatment of choice for patients with recurrent atrial
flutter is radiofrequency catheter ablation

65. Atrial fibrillatons
• Atrial fibrillation is the most common sustained arrhythmia.
• It is marked by disorganized, rapid, and irregular atrial
activation. The ventricular response to the rapid atrial
activation is also irregular
• Typically the pulse rate will vary between 120 and 160 beats per
minute
• The ECG shows normal but irregular QRS complexes, fine
oscillations of the baseline (so-called fibrillation or f waves) and
no P waves

68. • When atrial fibrillation is due to an acute precipitating event
the provoking cause should be treated.
Acute management of AF –
• Conversion rates using a 200-J biphasic shock delivered
synchronously with the QRS complex typically are >90%.
• Pharmacologic therapy to terminate AF is less reliable. Oral
and/or IV administration of amiodarone or procainamide
has only modest success.
• Patients are anticoagulated ( warfarin) for 4 weeks before
cardioversion.

69. Procainamide
•Procaine derivative, quinidine like action
•Antivagas action is absent
•It is acetylated in liver to N- acetyl procainamide
•A/E
•Hypotension
•Hypersensitivity reaction
•SLE
•C/I
•QT prolongation
•AV block
•Myasthenia gravis
Dose is 0.5-1g oral or im f/b o.25-0.5g every 4-6 hour

70. Amiodarone
Iodine –
containing
Block K+ Na+ ,
Ca++ & β
HR & AV
nodal
conduction
QT
prolongation
Uses =VF, VT
& AF
 Arrhythmic
death in post
MI
5 mg/kg slow IV
infusion over 30-
60 min
A/E – heart block,
pulmonary, fibrosis
hepatitis, dermatitis,
corneal deposits &
thyroidism
Interaction –
digoxin,
warfarin &
phenytoin
Broad-spectrum antiarrhythmic drug

71. Ventricular tachycardia
• This is a potentially life-threatening arrhythmia because it may
lead to ventricular fibrillation, asystole, and sudden death.
• A condition in which an electrical signal is sent from the
ventricles at a very fast but often regular rate.
• If the fast rhythm self-terminates within 30 seconds, it is
considered a non-sustained ventricular tachycardia.
• If the rhythm lasts more than 30 seconds, it is known as a
sustained ventricular tachycardia

73. • In haemodynamically compromised - emergency
asynchronous defibrillation is done
• If hemodynamically stable - intravenous therapy with class I
drugs or amiodarone .
• First-line drug treatment consists of lidocaine (50-100 mg
i.v. over 5 minutes) followed by a lidocaine infusion (2-4 mg
i.v. per minute).
• VT in patients with structural heart disease is now almost
always treated with the implantation of an ICD to manage
anticipated VT recurrence
Treatment

74. Lidocaine
• Used IV because of extensive 1st pass metabolism
• Selectively acts on diseased or ischaemic myocardium
 Has no hemodynamic side effects
 CNS side effects
 Loading Dose – 1-2 mg /kg in 30 sec
• Maintenance Dose – 1-4mg/min
 Used for VT
 Propranolol ↑ its toxicity

75. Ventricular fibrillation
• A condition in which many electrical signals are sent from the
ventricles at a very fast and erratic rate. As a result, the
ventricles are unable to fill with blood and pump.
• This rhythm is life-threatening because there is no pulse and
complete loss of consciousness.
• It requires prompt defibrillation to restore the normal rhythm
and function of the heart.

76. Basic and advanced cardiac life support is needed
Implantable cardioverter-defibrillators (ICDs) are first-line
therapy in the management of these patients

77. Torsades pointes
• This is a type of short duration tachycardia that reverts to sinus
rhythm spontaneously.
• It may be Congenital or due to Electrolyte disorders and
certain Drugs
• It may present with syncopal attacks and occasionally
ventricular fibrillation.
• QRS complexes are irregular and rapid that twist around the
baseline. In between the spells of tachycardia the ECG show
prolonged QT interval

78. - correction of any electrolyte disturbances
– stopping of causative drug
– atrial or ventricular pacing
– Magnesium sulphate 8 mmol over 10-15 min for acquired
long QT interval
– IV isoprenaline in acquired cases
– B blockers in congenital types
– Patients who remain symptomatic despite conventional
therapy and those with a strong family history of sudden
death usually need ICD therapy
Treatment

79. Sinus Bradycardia
• Physiological variant due to strong vagal tone or atheletic
training.
• Rate as low as 50 at rest and 40 during sleep.
Common causes of sinus bradycardia include:
• Hypothermia, hypothyroidism, Drug therapy with beta-
blockers, digitalis and other antiarrhythmic drugs.
• Acute ischaemia and infarction of the sinus node (as a
complication of acute myocardial infarction).

81. Sick sinus syndrome
• Sick sinus syndrome is a group of arrhythmias caused by a
malfunction of the sinus node
• A condition in which the sinus node sends out electrical
signals either too slowly or too fast. There may be alternation
between too-fast and too-slow rates.
• This condition may cause symptoms if the rate becomes too
slow or too fast for the body to tolerate.
• Bradycardia-tachycardia syndrome is a variant of sick sinus
syndrome in which slow arrhythmias and fast arrhythmias
alternate. It is often associated with ischaemic heart disease
and valvular lesions

82. • Artificial pacemakers have been used in the treatment of sick
sinus syndrome.
• Bradyarrhythmias are well controlled with pacemakers,
while tachyarrhythmias respond well to medical therapy.
• However, because both bradyarrhythmias and
tachyarrhythmias may be present, drugs to control
tachyarrhythmia may exacerbate bradyarrhythmia.
Therefore, a pacemaker is implanted before drug therapy is
begun for the tachyarrhythmia.

83. Atrio ventricular block

84. First degree heart block
• PR interval is lengthened beyond 0.20 seconds.
• In first-degree AV block, the impulse conducting from atria
to ventricles through the AV node is delayed and travels
slower than normal
• Seldom of clinical significance, and unlikely to progress

85. Second degree A-V Block
Mobitz type I (Wenckebach phenomenon):
• Gradually increasing P-R intervals culminating in an omission.
• When isolated, usually physiological and due to increased
vagal tone and abolished by exercise and atropine.
Mobitz type II
• The P wave is sporadically not conducted. Occurs when a
dropped QRS complex is not preceded by progressive PR
interval prolongation.
• Pacing is usually indicated in Mobitz II block, whereas patients
with Wenckebach AV block are usually monitored.

87. • Common in elderly age groups due to idiopathic bundle branch
fibrosis.
• Other causes include coronary heart disease, calcification from
aortic valve, sarcoidosis or it may be congenital.
• ECG shows bradycardia, P wave continues which is unrelated
to regular slow idioventricular rhythm.
• Treatment is permanent pacing.
Third degree AV block

89. Cardioversion
• Cardioversion is a medical procedure by which an abnormally
fast heart rate is converted to a normal rhythm using electricity.
• Two electrode pads are used. These are connected by cables to
a machine which has the combined functions of an ECG
display screen and the electrical function of a defibrillator.
• A synchronizing function allows the cardioverter to deliver a
reversion shock, by way of the pads, of a selected amount
of electric current over a predefined number of milliseconds at
the optimal moment in the cardiac cycle which corresponds to
the R wave of the QRS complex on the ECG.

90. • ABLATION THERAPY
This procedure involves the insertion of a thin wire
catheter into a blood vessel in the groin, arm, or neck, which
is then guided to the heart. Radiofrequency energy is then
delivered to ablate tissue in the heart
• IMPLANTABLE DEVICES
– Pacemaker
– Implantable Cardioverter-Defibrillator
• SURGERY
– Maze procedure
– Coronary bypass

91. The Pacemaker

92. New developments
Agents Similar to Amiodarone
• Dronedarone, budiodarone, celivarone
Others
• Ranolazine, vernaklant, ivabradine
• Adenosine A1 receptor agonist
Nutritional alternatives
• Berberine, coenzymeQ10, taurine,

93. Alternative therapies
• Acupuncture
• Mediterrian diet
• Lifestyle changes
• Targeted natural therapies
– Omega 3/fish oil
– Magnesium and potassium
– Hawthorn
– Antioxidants like n-acetyl cysteine, vitamin C & E and co
enzyme Q10

94. New targets
• Specific acetylcholine-regulated K+ current inhibition
• Abnormal calcium handling
• Gap junction modification
• Na+/Ca+ exchanger inhibition
• Stretch-induced or ischemia-induced ATP-sensitive
K+ current inhibitors
• Gene and cellular therapy

95. conclusion
• Death resulting from disruptions within the electrical pathways
that control heart rhythm contribute to over 400,000 deaths
each year.
• While anti arrhythmic drugs are effective, they are also
expensive and can have serious side effects, not the least of
which is a tendency to initiate the very event being treated.
• So the alternative therapies should be considered targeted and
developed as well as the development of newer antiarrhythmic
drugs to overcome the disadvantages of the present drugs is
demanded in the present situation.

96. Thank you