Pathophysiology of arrhythmias and its pharmacotherapy

1. Arrhythmias
RVS Chaitanya koppala

2. Normal cardiac electrophysiology
• Normal cardiac rhythm, sinus rhythm is characterized by contraction
of first atria and ventricles (Systole) followed by relaxation (diastole)
during with the heart fill with blood before the next cardiac cycle
begins
• Above mention sequence is maintained by electrical activity of heart’s
• Myocytes are electrically active and capable of generating action
potential.
• Adjacent myocytes form the connections with the adjacent myocytes
through channels / protein channels called gap junctions

3. Cardiac action potential
• Understanding of ionic basis of the cardiac action potential is
important (?)
• Inherited abnormalities of ion channels functions (channelopathies)
are an important cause of sudden cardiac death (?)
• Phospholipid membrane of the cardiac myocytes is spanned by
numerous proteins = ion channels
• Permeablility to specific ions= diastolic depolarization + resting
membrane potential+ pacemaker activity + action potentials

4. • Resting membrane potential is -60 to -90 mV (more intracellular than
extracellular (?) bcz of Na+/k+ - ATPase
• Which pumps K+ ions into cell in exchange for Na+ ions,
• Pumps K+ ions out of the cell with unaccompanied by anions resulting
in the net loss of charge and thus a negative resting/ diastolic/phase 4
• Specialised myocytes form the cardiac conduction system and these
cell have pacemaker activity
• Influenced by sympathetic nervous system ( Camp) and
parasympathetic nervous system by circulating catecholamines

6. Refractoriness
Action potential of cardiac myocytes differs from that seen in nerve
cells by the presence of a plateau phase (myocyte is inexictable and
refractory)
The time interval b/n the onset of the action potential and the
regaining of the electrical excitability is known as the refractory period
“Drugs that prolong the action potential duration (APD) prolong the
refractory period”

7. Normal cardiac conduction

8. Normal electrocardiogram (ECG)

9. Arrhythmia mechanisms
Causes
• Abnormal impulse formation
• Abnormal impulse propagation

10. Abnormal impulse formation
Abnormal automaticity:
Another term for pacemaker activity
Rate of firing of pacemaker is largely determined by the duration of
the phase 4 (?)
PHASE 4: determined by
1. Max diastolic potential following repolarisation of preceeding AP
2. Slope of the diastolic depolarization (pacemaker currents)
3. Threshold potential for generation of a new action

12. Trigger activity
• Describes impulse formation dependent upon after depolarization
• EADs (During phase 2/3)
• DADs (During Phase 4)
• In both cases after depolarization may reach the threshold potential
required for generation of a new action potential
EADs DADs
Congenital and acquired long QT syndromes Reperfusion following ischaemia, heart failure,
digitalis toxicity and catecholamine
polymorphic VT
Prolonged APD promotes reactivation of the
inward calcium currents
Spontaneous release of calcium in burst by
Sarcoplasmic reticulum
Activation of Na+/Ca2+ EXCHANGER

14. Abnormal impulse propagation
Re-entry: many clinically arrhythmias are due to re- entry in which an
activation wave front rotates continuously around a circuit
Precise set of electrophysiological conditions must be met in order for
re – entry to occur
1. premature beat must encounter unidirectional condition
2.Central non conducting obstacle around which re entry circuit
develops
3. Conduction proceed slowly enough down the other limb
4. Circulating wave front activation must continue to encounter
electrically excitable tissue

16. Clinical problems
Patients with cardiac arrhythmia may present with a number of symptoms
Palpitations Sudden drop in cardiac output
Sinus tachycardia Dizziness, syncope, sudden death
Reduced cardiac output Atrial tachyarrhythmias/ flutter
Reduced exercise capacity Atrial fibrillation
Breathlessness
Fatigue
Angina
Myocardial infarction

17. Arrhythmias may aggravate heart failure in two ways:
1. Haemodynamic effect of the arrhythmia (heart failure or
aggravate existing heart failure)
2. Prolonged tachycardia or any type may lead to (tachycardia
induced cardiomyopathy)

18. Diagnosis
1. DETAILED HISTORY SHOULD BE OBTAINED
2. HISTORY OF CARDIAC DISEASE
3. OTHER DIAGNOSED MEDICAL CONDITION
4. A FULL DRUG HISTORY (Both OTC/Rx)
5. A FAMILY HISTORY OF HEART FAILURE
6. A FAMILY HISTORY OF SUDDEN DEATH

19. Mandatory investigation includes
1.12-LEAD ECG
2. ECHOCARDIOGRAM
3.AMBULATORY ECG (recording for up to 7days)
4. Infrequent symptoms an event recorder, ECG strips, Insertable loop
recorder

20. Management
• Pathological tachycardia is conventionally defined as resting heart
rate over 100/min
• Classified as two types
1. SVT (?)
2. VT(?)

21. SVT
INAPPROPRIATE SINUS
TACHYCARDIA
12 LEAD ECG, AMBULATORY ECG,
ECHO CARDIOGRAPHY
Beta blockers, verapamil, ivaradine
ATRIAL FLUTTER Right atrial tachycardia with re
entry ( 300/min) 1:2 ratio av
conduction
Beta blocker, verapamil, diltiazem
and digoxin,
1:1- sotalol, amiodarone
FOCAL ATRIAL TACHYCARDIA Uncommon arrhythmia discharge
of focal source within the atria and
surrounding venous structures
Adenosine, class ic, 1:1 av
conduction,
JUNCTIONAL RE ENTRY
TACHYCARDIA
SVT Used to explain JRT
TWO TYPE
AVNRT
AVRT
Intravenous adenosine 12 mg
Intravenous verapamil 5 mg
Prophylactic drugs: Beta blockers,
verapamil, flecainide and sotalol

23. Atrial fibrillation :
• Most common sustained arrhythmia
• Classified as:
1. Paroxysmal – episodes of AF lasting no more than 7days
2. Persistent- more than 7days
3. Longstanding persistant – more than 7 year
4. Permanent- no decision has been made not to attempt cure of persistant AF
Therapy
1. ANTICOAGULANT THERAPY
2. INTRAVENOUS Beta blockers, verapamil and digoxin
3. Several class I (sotalol and amiodarone)
4. Class Ic flecainide and class III amiodarone