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 potential ECF: extracellular fluid ICF: intracellular 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
Management 3. Assess risk High risk Moderate risk Low risk
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
Management strategies Termination Conversion of SVT to SR Amelioration Increasing AVB in AF Pacing AVB Prevention Decrease or abolish arrhythmia attacks Cure Ablation of irritable focus or accessory pathway
Management strategies Termination Conversion of SVT to SR Amelioration Increasing AVB in AF Pacing AVB Prevention Decrease or abolish arrhythmia attacks Cure Ablation of irritable focus or accessory pathway
Management strategies Termination Conversion of SVT to SR Amelioration Increasing AVB in AF Pacing AVB Prevention Decrease or abolish arrhythmia attacks Cure Ablation of irritable focus or accessory pathway
Management strategies Termination Conversion of SVT to SR Amelioration Increasing AVB in AF Pacing AVB Prevention Decrease or abolish arrhythmia attacks Cure Ablation of irritable focus or accessory pathway
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 External electric therapy Anti-arrhythmic drugs Non-pharmacologic therapy
Management modalities Non-pharmacologic therapy 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 No good classification scheme exists!! Vaughan Williams (1970) Effect on the action potential of cardiac cells Sicilian Gambit (1990) Effect on the ionic currents of cardiac cells
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
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