Supraventricular

Arrhythmias

Iris G.
Canlas
Section 2A
Cardiac
Electrophysiology
Cardiac
Electrophysiology
Impulse
propagation – Normal Rate: 60-
100 bpm
Cardiac
Electrophysiology
Cardiac
Electrophysiology
Arrhythmia
• Abnormal impulse generation
• Abnormal impulse conduction
• Both
Arrhythmia
• Classification of Arrhythmias
• According to location
– Supraventricular arrhythmia
– Ventricular arrhythmia
• According to rate or rhythm
– Tachycardia or tachyarrhythmia
– Bradycardia or bradyarrhythmia
Arrhythmia
 Reentry mechanism
• For reentry to occur, certain
conditions must be met that are
related to the following:
– the presence of a unidirectional block
within a conducting pathway
– critical timing
– the length of the effective refractory
period of the normal tissue
 Reentry mechanism
• Reentry (bottom panel) can occur if
branch 2 has a unidirectional block.
When this condition exists, an
action potential will travel down the
branch 1, into the common distal
path (branch 3), and then travel
retrograde through the
unidirectional block in branch 2
(blue line).
• When the action potential exits the
block, if it finds the tissue excitable,
then the action potential will
continue by traveling down but if it
finds the tissue unexcitable (i.e.,
within its effective refractory
period), then the action potential
will die.
 Reentry mechanism
• Because both timing and refractory state of
the tissue are important for reentry to occur,
alterations in timing (related to conduction
velocity) and refractoriness (related to
effective refractory period) can either
precipitate reentry or abolish reentry.
• For this reason, antiarrhythmics that shorten
conduction velocity and prolongs
refractoriness are used in the management of
reentrant arrhythmias.
Supraventricular
Arrhythmia
• Atrial fibrillation
• Atrial flutter
• Supraventricular tachycardia
Atrial Fibrillation
• Atrial fibrillation is the most common
irregular heart rhythm encountered in clinical practice
• The impulses (400-600 bpm) spread chaotically and
compete for a chance to travel through the AV node
leading to a rapid and disorganized heartbeat.
• It is strongly associated with established cardiovascular
risk factors (eg. CAD, HTN, and diabetes) and advancing
age.
• Structural heart disease, acute or chronic alcohol use,
illicit drug use, and hyperthyroidism
Atrial Fibrillation
• AF is caused by
multiple reentrant
waveforms
within the atria,
which bombard the
atrioventricular (AV)
node, commonly
leading to a
tachycardia that is
irregularly irregular.
Atrial Flutter
• Atrial flutter (AFL) is the second most
common tachyarrhythmia, after atrial fibrillation.
• Patients at highest risk for atrial flutter include those with
long-standing hypertension, valvular heart disease
(rheumatic), left ventricular hypertrophy, coronary artery
disease with or without depressed left ventricular
function, pericarditis, pulmonary embolism,
hyperthyroidism, and diabetes.
 Atrial Flutter
• AF is caused by a reentrant
circuit that is confined to the
right atrium (RA).
• The impulses travel through
the atrial septum, then across
the right atrium, then inferiorly
through the right atrium free
wall, and then back across
through an isthmus bounded
by the coronary sinus os and
the tricuspid valve annulus.
 Supraventricular
Tachycardia
• Characterized by a rapid heart rate that
ranges between 100 and 240 beats per minute which
originates from above the ventricle.
• SVT can frequently be precipitated by exercise, stress, fever,
or drug exposure (e.g., cold medications, digitalis, asthma
medication, cocaine, alcohol, caffeine) as well as a number
of medical conditions, such as atherosclerosis, heart failure,
thyroid disease, chronic lung disease, pneumonia,
pulmonary emboli, and pericarditis.
Supraventricular
Tachycardia
• Re-entry tachycardia
is the most common
mechanism for SVT.
• It involves an extra
electrical circuit
rhythm start up
elsewhere in the the
atria and overrides
the natural
pacemaker.
Management
• Non-pharmacologic
– Electrical cardioversion
– Catheter ablation
– Physical maneuvers that enhance vagal
activity (SVT)
• Pharmacologic
– Antiarrhythmics
– Anticoagulants
Pharmacologic
Treatment
• Goal of treatment:
– controlling the heart rate
– regaining a normal heart rhythm (sinus
rhythm)
– reduction of subsequent
thromboembolism and stroke risks
 Classification of Drug Mechanisms of Action Comment

IA Sodium channel blocker Slows Phase 0 depolarization

(Qunidine, Procainamide,
Disopyramide)

IB Sodium channel blocker Shortens Phase 3 repolarization

(Lidocaine, Mexilitine, Tocainide)

IC Sodium channel blocker Markedly slows Phase 0

(Flecainide, Propafenone) depolarization

II Beta-adrenoceptor blocker Suppresses Phase 4 depolarization

(Propranolol, Metoprolol, Esmolol,
Pindolol)

III Potassium channel blocker Prolongs Phase 3 repolarization

(Sotalol, Bretylium, Amiodarone)

IV Calcium channel blocker Shortens action potential

(Verapamil, Diltiazem, Nifedipine)
Rate Control
• Beta blockers
• Calcium channel blockers
• Digoxin
• Adenosine
Rate Control
• Beta blockers
– Blocks beta-adrenergic receptors
– Diminish phase 4 depolarization thereby
prolonging AV conduction and decreasing heart
rate and contractility
• Propranolol - competitively blocks β1- and β2-
receptors
• Esmolol and metoprolol - cardioselective
Beta Blockers
• Pharmacokinetics
– Absorbed readily and completely from
the GI tract (oral)
– Protein binding: Propranolol (90%),
Metoprolol (12%), Esmolol (55%)
– Metabolized in the liver
– Excretion via urine (as metabolites and
small amounts of unchanged drug)
– Duration: Metoprolol (10-20 hr), Esmolol
(10-30 min)
 Beta Blockers
• Clinical use
– Hypertension, Heart failure, Cardiac arrhythmias, angina
pectoris, Hyperthyroidism,migraine, acute MI
• Dosage
– Metoprolol: 100-200 mg daily
– Propranolol: 30-160 mg/day in divided doses
– Esmolol (IV): Loading dose: 500 mcg/kg; Maintenance: 50
mcg/kg/min for 4 mins.
• ADR
– Bradycardia, hypotension, bronchospasm (propranolol),
arterial insufficiency, chest pain, CHF, edema, palpitation,
syncope, impotence, nausea, diarrhea, insomnia, short-term
memory loss, nightmares
Beta Blockers
• DI
– Hypotension or marked bradycardia with catecholamine
depletors.
– Increased risk of bradycardia, AV block, hypotension and
CHF with IV calcium channel blockers.
– May increase effects of hypoglycemics.
• Contraindication
– Uncontrolled heart failure, marked hypotension, severe
bradycardia and heart block, cardiogenic shock, severe
peripheral arterial circulatory disorders, asthma
Rate Control
• Calcium channel blockers
– Decrease inward current carried by calcium,
resulting in a decrease in the rate of Phase 4
depolarization and slowed conduction in the AV
node, as well as relax vascular smooth muscle
• Verapamil: heart > smooth muscles
• Diltiazem: intermediate
* Nifedipine: smooth muscles > heart
Calcium channel Blockers
• Pharmacokinetics
– Rapidly and almost completely absorbed
from the GI tract (oral).
– Distributed into breast milk and highly
protein bound (80-90%)
– Extensively metabolized in the liver
– Excreted by the kidney (70% of dose) as
metabolites and via bile into feces (16%).
 Calcium channel Blockers
• Clinical Use
– Supraventricular arrhythmias, Hypertension, Angina Pectoris
• Dosage
– Diltiazem: Initially, 250 mcg/kg by bolus IV Inj over 2 mins, if
necessary, after 15 min, may administer another dose of 350 mcg/kg.
– Verapamil: 120-480 mg/day in 3-4 divided doses
IV: Initially, 5-10 mg; may give 10 mg 30 mins after initial dose,
if needed.
Calcium channel Blockers
• ADR
– Bradycardia, hypotension, hyperprolactinemia
(verapamil), gingival hyperplasia (nifedipine & diltiazem),
hepatotoxicity
• DI
– Decreased levels/effects with CYP3A4 inducers
– Increased levels/effects with CYP3A4 inhibitors
• Contraindication
– Acute MI, cardiogenic shock, acute unstable angina,
Severe congestive cardiac failure, Pregnancy and
lactation.
Rate Control
• Digoxin
– a cardiac glycoside which has positive
inotropic activity .
– reduces the conductivity of the heart
through the atrioventricular (AV) node.
– exerts direct action on vascular smooth
muscle and indirect effects mediated
primarily by the autonomic nervous
system and an increase in vagal activity.
 Digoxin
• Pharmacokinetics
– Absorption from the GI tract is variable.
– Widely distributed in tissues, including the
heart, brain, erythrocytes, and skeletal
muscle. 20-30% bound to plasma proteins.
– Excreted mainly unchanged.
• Clinical Use
– Supraventricular arrhythmias (used to control
ventricular response rate in AF and AFl ),
heart failure
 Digoxin
• Dosage
– Loading dose of 0.75-1.5 mg during the first 24-hr period as a
single dose or in divided doses every 6 hr for less urgent or
greater risk cases.
– Usual maintenance: 125-250 mcg daily but may range from
62.5-500 mcg daily.
• ADR
– Cardiac arrhythmias in combination with heart block, nausea
and vomiting, confusion, dizziness, nervousness, agitation and
amnesia, visual disturbances, gynecomastia, rapid IV admin
may lead to vasocostriction and transient hypertension
• DI
– Electrolyte imbalances such as hypokalaemia and
hypomagnesemia (e.g. admin of potassium-losing diuretics,
corticosteroids) can increase the risk of cardiac toxicity.
 Digoxin
– Metoclopramide may alter the absorption
of solid dosage forms of digoxin.
– Blood levels increased by calcium channel
blockers, spironolactone, quinidine, and
calcium salts.
• Contraindication
– Digitalis toxicity, ventricular
tachycardia/fibrillation, obstructive
cardiomyopathy. Arrhythmias due to
accessory pathways (e.g. Wolff-Parkinson-
White syndrome).
Rate Control
• Adenosine
– acts rapidly to slow down conduction
through the AV node via the A1
receptors.
– mediates peripheral and coronary
vasodilatation by stimulating the A2
receptors.
– DOC in SVT
 Adenosine
• Pharmacokinetics
– Rapidly taken up into the erythrocytes and vascular
endothelial cells.
– Metabolised to adenosine monophosphate and inosine.
– Plasma half-life: <10 sec.
• Clinical Use
– Supraventricular tachycardia, Paroxysmal
supraventricular tachycardia, Myocardial imaging
• Dosage:
– Initially, 3 mg by rapid IV inj into a central or large
peripheral vein over 2 sec with cardiac monitoring; 6 mg
may be given after 1-2 minutes if necessary
Adenosine
• ADR
– Facial flushing, palpitations, bradycardia, sweating,
hypotension, dyspnea, headache, lightheadedness, numbness,
neck and back pain, nausea, metallic taste.
• DI
– Adenosine effects antagonised by methylxanthines
– Adenosine effects are potentiated by dipyridamole.
• Contraindication
– 2nd or 3rd degree AV block and sick sinus syndrome (unless
pacemaker fitted), asthma, hypersensitivity.
Rhythm Control
• Class IA
• Class IC
• Class III
 Rhythm Control
• Class IA (quinidine, procainamide,
disopyramide)
– Blocks open or inactivated sodium channels
→ slow Phase 0 depolarization → prolong
action potential and slow conduction velocity
– Also decreases slope of Phase 4
spontaneous depolarization → decrease
automaticity
 Class IA
• Pharmacokinetics
– Rapidly absorbed from the GI tract.
– Crosses the placenta and passes into the breast milk.
– Metabolized mainly by cytochrome CYP450 isoenzymes in
the liver
• A portion of Procainamide is acetylated to form N-
acetylprocainamide which prolongs action potential (Class III)
– Excreted in the urine via active renal secretion.
• Clinical Uses
– Supraventricular and ventricular arrhythmias, maintain
sinus rhythm after direct cardioversion of AF or AFl
 Class IA
• Clinical Uses
– Supraventricular and ventricular arrhythmias,
maintain sinus rhythm after direct cardioversion
of AF or AFl
• Dosage
– Quinidine
• 400-600 mg 2-3 hrly until paroxysm is terminated.
• 200 mg 2-3 hrly for 5-8 doses for AF
• As gluconate: 800 mg via infusion. Max total IV dose: 10 mg/kg.
– Procainamide
• 100 mg every 5 mins until arrhythmia has been suppressed or a
max of 1 g has been reached.
Class IA
– Disopyramide
• PO 300-800 mg/day in divided doses.
• IV 2 mg/kg (max: 150 mg), followed by 200 mg
via oral admin after completion of inj.
• ADR
– Proarrhythmia, Severe hypotension, nause,
vomiting, diarrhea, Drug-induced SLE
syndrome (Procainamide), cinchonism
(Quinidine), anticholinergic activity
(Disopyramide)
Class IA
• DI
– May enhance effects of antihypertensives,
other antiarrhythmics, anticholinergics
and neuromuscular-blocking drugs and
diminish those of parasympathomimetics.
• Contraindication
– Hypersensitivity, complete heart block,
digitalis intoxication, SLE, heart failure,
hypotension, lactation, myasthenia gravis
 Class IC
• Flecainide and Propafenone
– Blocks open or inactivated sodium channels
→ markedly slow Phase 0 depolarization in
Purkinje and myocardial fibers → slow
conduction velocity
– Reduce automaticity by increasing threshold
potential
Class IC
• Pharmacokinetics
– Readily and well-absorbed from the GI tract (oral).
– Flecainide 40% protein bound; Propafenone 95 %
protein bound
– Metabolized in the liver, Flecainide partly in the
kidneys
– Mainly excreted in the urine, about 30% as
unchanged drug. About 5% is removed in the feces.
• Clinical Use
– Supraventricular and ventricular arrhythmias
 Class IC
• ADR
– Exacerbation of arrhythmia, metallic taste and
constipation(Propafenone), corneal deposits,
pulmonary fibrosis, skin reactions(Flecainide)
• DI
– Effects of flecainide may be increased by
concurrent admin of amiodarone, cimetidine,
cisapride, and propanolol
– Reduced plasma levels of Propafenone when
used with enzyme inducers and increased with
enzyme inhibitors
Class IC
• Contraindication
– Uncontrolled heart failure, marked
hypotension, severe bradycardia and
heart block, conduction abnormalities,
cardiogenic shock, myasthenia gravis.
 Class III
• Sotalol, Dofetilide, Amiodarone
– Blocks potassium channels → prolongs Phase 3
repolarization without altering Phase 0
• Pharmacokinetics
– Almost completely absorbed from the GI tract (oral);
amiodarone (variable)
– Amiodarone and Sotalol crosses the placenta and enters
breast milk and has high protein binding; Dofetilide has low
protein binding
– Hepatic metabolism
• Major metabolite of amiodarone, desethylamiodarone, is bioactive
– Amiodarone excreted mainly in the feces; Sotalol and
Dofetilide in the urine
 Class III
• Clinical Use
– Maintenance or restoration of sinus rhythm in
atrial fibrillation, Serious ventricular
arrhythmias and supraventricular
arrhythmias
• ADR
– Blue-grey discolouration of skin,
photosensitivity, hyper- or hypothyroidism
(Amiodarone), Torsade de pointes(Dofetilide),
asthma and impotence(Sotalol), bradycardia,
Heart block, heart failure, hepatotoxicity
 Class III
• DI
– Many, based on CYP metabolism 
– Dofetilide: Additive with other QT-prolonging
drugs
• Contraindications
– Amiodarone: Hypersensitivity to amiodarone or
iodine, cardiogenic shock, pregnancy
– Sotalol: Bronchospasm, asthma, history of
obstructive airways disease
– Dofetilide: Hypersensitivity, Congenital or
acquired long QT syndromes.
Anticoagulant Therapy
• Disruption of normal atrial
electromechanical function in atrial
fibrillation → blood pooling and blood
stasis → thrombus formation →
thromboembolism → stroke
• Anticoagulant or antiplatelet therapy
medications can reduce the risk of
blood clots and stroke, but, they do
not completely eliminate the risk.
Anticoagulant Therapy
• Warfarin
– inhibits synthesis of vit K-dependent
coagulation factors VII, IX, X and II and
anticoagulant protein C and its cofactor
protein S
– Absorbed readily from the GI tract (oral)
– Extensive (99%) protein binding and
crosses placenta
– Hepatic metabolism
– Excreted via urine
Anticoagulant Therapy
• Clinical Use
– Treatment and prevention of venous thromboembolism
• ADR
– Hemorrhage, skin changes or discoloration, purple
toes and fingers, diarrhea, jaundice, nausea, vomiting,
hepatic dysfunction, pancreatitis
• DI
– Avoid major changes in dietary intake of Vit K
– Many, based on CYP metabolism
– Drugs that are highly protein bound may displace
warfarin from binding
Anticoagulant Therapy
• Contraindications
– Hemorrhagic tendencies or blood dyscrasia;
recent surgery; peptic ulcer; severe
hypertension; threatened abortion;
alcoholism; severe renal and hepatic
impairment; pregnancy.