Cardiac Arrhythmias

For Pharmacists

Agenda

Overview of the normal

Classification

Management

Therapy

Conclusion

Cardiac arrhythmias

Overview of the normal

Arrhythmia: definition

From the Greek a-, loss + rhythmos, rhythm

= loss of rhythm

Any variation from the normal rhythm of the heartbeat

encompassing abnormalities of:

Rate: too slow (bradycardia) or too fast (tachycardia)

Regularity

Site of impulse origin

Sequence of activation

Any rhythm that is not normal sinus rhythm

Normal sinus rhythm

Temporal sequence of activation

Temporal sequence of activation

Shape of action potential

Normal cardiac automaticity

Normal cardiac automaticity

All cardiac cells have property of self-excitation ie

INTRINSIC RHYTHMICITY

They can therefore spontaneously depolarize

Pacing of the heart will be carried out by cells with the

fastest natural rate ie OVERDRIVE SUPPRESSION

Currents responsible for ventricular AP.Length of the arrows shows the relative size of each ionic current.

E: Equilibrium potentialECF: extra-cellular fluidICF: intra-cellular fluid.

Cardiac arrhythmias

Classification

Arrhythmias: classification

Site of origin

Mechanism

Duration

Clinical

significance

Site of origin

Supra-ventricular:

Sinus node

Atria

Atrio-ventricular junction

(above bifurcation of HB)

Ventricular:

Bundle branches

Purkinje fibres

Working myocardium

Mechanism

Abnormal impulse initiation

Abnormal automaticity

Triggered activity

Abnormal impulse conduction

Slow or blocked conduction

Re-entry

Most clinically important

arrhythmias are due to re-entry

Re-entry

Re-entry

Duration

Paroxysmal or non-sustained

Persistent or sustained

Permanent or chronic

Clinical significance

Benign

No independent increase in risk

Significant

Independent increase in risk

Potentially lethal

Can lead to proximate fatality if left untreated

Cardiac arrhythmias

Management

Management

1. Precise diagnosis + assessment

Must precede any intervention!!

2. Eliminate precipitants

Drugs: digoxin, beta-blockers

CHF, TTX, anxiety

Hypokalaemia, hypoxia, acidosis

3. Assess risk

High risk

Moderate risk

Low risk

Management

Low risk arrhythmias

Do not have potential to produce death

Need not be suppressed

Treat only if they produce disruptive symptoms

High risk arrhythmias

Potentially life-threatening

Must be suppressed

Treat always even if symptoms are minor

Moderate risk arrhythmias

Problematic!

No clear cut treatment of choice

Amelioration

Prevention

Cure

Management strategies

Termination

• Increasing AVB in AF

• Pacing AVB

• Decrease or abolish

arrhythmia attacks

• Ablation of irritable focus or

accessory pathway

• Conversion of SVT to SR

Amelioration

Prevention

Cure

Management strategies

Termination

• Increasing AVB in AF

• Pacing AVB

• Decrease or abolish

arrhythmia attacks

• Ablation of irritable focus or

accessory pathway

• Conversion of SVT to SR

Amelioration

Prevention

Cure

Management strategies

Termination

• Increasing AVB in AF

• Pacing AVB

• Decrease or abolish

arrhythmia attacks

• Ablation of irritable focus or

accessory pathway

• Conversion of SVT to SR

Amelioration

Prevention

Cure

Management strategies

Termination

• Increasing AVB in AF

• Pacing AVB

• Decrease or abolish

arrhythmia attacks

• Ablation of irritable focus or

accessory pathway

• Conversion of SVT to SR

External electric therapy

Anti-arrhythmic drugs

Non-pharmacologic therapy

Management modalities

Autonomic manoeuvers

External electric therapy

Anti-arrhythmic drugs

Non-pharmacologic therapy

Management modalities

Autonomic manoeuvers

External electric therapy

Anti-arrhythmic drugs

Non-pharmacologic therapy

Management modalities

Autonomic manoeuvers

External electric therapy

Anti-arrhythmic drugs

Non-pharmacologic therapy

Management modalities

Autonomic manoeuvers

Non-pharmacologic therapy

Management modalities

Radio-frequency ablation

Arrhythmia surgery

Implantable devices

Cardiac arrhythmias

Pharmacotherapy

Bradyarrhythmias

Bradyarrhythmias

Identify and treat the cause eg hypothyroidism

Atropine (anti-cholinergic)

Decreases vagal tone

Decreases AV block and increases SA rate

Sympathomimetics: isoprenaline or adrenaline

Increase heart rate and contractility:

ß1 adrenergic effect

Bradyarrhythmias

Bradyarrhythmias

Bradyarrhythmias

Tachyarrhythmias

Aims of drug treatment

1. Afford symptomatic relief

2. Prevent onset of arrhythmias producing

major haemodynamic sequelae

3. Prevent recurrent life-threatening

arrhythymias

Ideal anti-arrhythmic drug

1 Wide range of therapeutic activity against

atrial, junctional and ventricular arrhythmias

2 Available in parenteral and oral form

3 Pharmacokinetic properties to allow predictable long

term plasma level

4 No pro-arrhythmic, no depressant haemodynamic

effects or significant non-cardiac side-effects

Ideal anti-arrhythmic drug

1 Wide range of therapeutic activity against

atrial, junctional and ventricular arrhythmias

2 Available in parenteral and oral form

3 Pharmacokinetic properties to allow predictable long

term plasma level

4 No pro-arrhythmic, no depressant haemodynamic

effects or significant non-cardiac side-effects

Torsades de pointes

http://crediblemeds.org/

Once upon a

time……

Back in 1986……

Back in 1986……

Back in 1986……

CAST

A causes B

PVCs in post-MI patients increase mortality

C reduces A

AAD (encainide, flecainide, and moracizine) can successfully

reduce PVCs

C therefore reduces B

AADs in post-MI patients with PVCs reduces mortality

CAST

“Prophylactic” treatment of

PVCs in post-MI patients

CAST

Drugs used: encainide,

flecainide, and

moracizine

Successful reduction in

the amount of PVCs

BUT: led to more

arrhythmia-related

deaths

CAST

Total mortality was

significantly higher

in actively treated

group compared to

placebo

Excess mortality

was attributed to

proarrhythmic

effects of the agents

AFFIRM

Rate or rhythm control in AF

AFFIRM How do you interpret this?

Classification of AADs

Vaughan Williams (1970)

Effect on the action potential of cardiac cells

Sicilian Gambit (1990)

Effect on the ionic currents of cardiac cells

No good classification scheme exists!!

General considerations

Continuing imperfections of current AADs and rapidly

expanding technologies have led to:

Rapid expansion in use of devices and ablation techniques for

treatment of arrhythmias

Rapid disappearance of many AADs (some of which are no

longer manufactured!!)

Cardiac arrhythmias

Non-pharmacological therapy

EPS

RF Ablation

RF energy is delivered to a

localised area of cardiac tissue

from the tip of a steerable

electrode catheter

RF Ablation

Arrhythmia trigger/substrate is modified:

Initiating foci are destroyed

Conducting pathways are interrupted

No painful skeletal muscle contraction occurs

Can be carried out under LA

Serious complications seldom occur

Non reversible, permanent cure

Uniformly high success rate (depends on arrhythmia type)

RF Ablation lesions

RF Ablation

Useful for:

AVNRT and AVRT

Atrial tachycardia

Atrial flutter

Bundle branch re-entry

VT in normal hearts

Conclusions

Remember…..

Conclusions - 1

An arrhythmia is any rhythm that is not sinus rhythm

Ionic flows through

membrane channels

determine automaticity,

conduction and excitability

Conclusions - 2

Arrhythmias may be classified by:

Site of origin

Mechanism

Duration

Clinical significance

Conclusions - 3

Management depends on:

Precise diagnosis

Elimination of precipitants

Risk assessment

Conclusions - 4

Pharmacotherapy is:

Imperfect

May be dangerous

RF ablation and devices are

rapidly becoming the

mainstay of treatment

Confidential –

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Thank you for your attention!

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