Cardiac Arrhythmias

Core

Introduction

An arrhythmia is any disturbance of the rate, rhythm or conduction of the electrical impulse through the heart. Some are entirely benign (occasional atrial ectopics in healthy adults); others are immediately life-threatening (ventricular fibrillation). Pharmacology lies at the centre of the management of nearly all of them, and the principles are easier to learn than the long list of drugs first suggests.

This article assumes the cardiac electrophysiology covered in Cardiac Conduction and Contraction, the ECG basics in Electrocardiograms, and the mechanisms of arrhythmogenesis in Electrocardiogram Pathology.

A Brief Electrophysiology Recap

Two distinct cardiac action potentials need to be remembered, because the antiarrhythmic drugs target different phases of each.

The Fast Cardiac Action Potential

This is the action potential of working atrial and ventricular myocytes. It has five phases:

• Phase 0: Depolarisation. Voltage-gated sodium channels open, sodium rushes in, and the membrane potential rapidly swings positive.
• Phase 1: Initial repolarisation. Sodium channels inactivate; transient outward potassium currents briefly partly repolarise the cell.
• Phase 2: Plateau. Inward calcium current through L-type calcium channels balances outward potassium current. The plateau is the cardiac action potential's distinguishing feature, and it is responsible for the long refractory period that prevents tetany.
• Phase 3: Repolarisation. Calcium channels close; potassium channels are now dominant; the cell repolarises.
• Phase 4: Resting potential. The Na⁺/K⁺ ATPase restores the resting ionic gradient.

The Slow (Pacemaker) Action Potential

This is the action potential of pacemaker tissue at the sinoatrial (SA) and atrioventricular (AV) nodes. It differs from the fast action potential in two ways:

• There is no stable resting potential: phase 4 is a slow, spontaneous depolarisation driven principally by the "funny" current (I_f), which is responsible for automaticity.
• Phase 0 depolarisation is mediated by L-type calcium channels, not sodium channels.

This is why calcium channel blockers and beta-blockers slow the heart at the SA and AV nodes, while sodium channel blockers act mainly on working myocardium.

Diagram: The fast cardiac action potential (working myocardium, sodium-driven phase 0) and the slow pacemaker action potential (SA/AV node, calcium-driven phase 0 with phase 4 funny-current automaticity), with the sites of action of the Vaughan-Williams antiarrhythmic classes labelled.

The Vaughan-Williams Classification

The classical classification by Miles Vaughan-Williams divides antiarrhythmic drugs into four classes by their action on the cardiac action potential. A useful memory aid is "Some Block Potassium Channels": in order, Sodium, Beta-blocker, Potassium, Calcium.

Class I: Sodium Channel Blockers

Class I drugs block voltage-gated sodium channels in working myocardium, slowing phase 0 depolarisation. They are subdivided by their effect on action potential duration and the kinetics of channel binding:

• Class IA (e.g. quinidine, procainamide, disopyramide): intermediate dissociation; lengthen action potential duration. Largely historical in UK practice.
• Class IB (e.g. lidocaine): rapidly dissociating; preferentially block sodium channels in fast-firing or ischaemic tissue. Lidocaine is given intravenously and is used for ventricular tachycardia, particularly in the context of ischaemia. Side effects are predominantly central nervous system: dizziness, drowsiness and, in toxicity, seizures.
• Class IC (e.g. flecainide): slowly dissociating; markedly slow phase 0 in normal tissue, slow conduction throughout the heart. Flecainide is used orally as a "pill in the pocket" for paroxysmal atrial fibrillation in patients without structural heart disease, and is occasionally given intravenously for cardioversion. Strictly contraindicated after myocardial infarction (the CAST trial showed increased mortality) and in any patient with structural heart disease.

An important pitfall: flecainide can cause atrial flutter to conduct 1:1 through the AV node, producing a dangerous ventricular response. It must therefore be co-prescribed with an AV-nodal blocker (a beta-blocker or non-dihydropyridine calcium channel blocker).

Class II: Beta-Blockers

Beta-blockers reduce sympathetic drive, slowing phase 4 depolarisation in pacemaker tissue and prolonging conduction through the AV node. They lengthen the PR interval and reduce heart rate. The drugs licensed for arrhythmias in the UK are bisoprolol, atenolol, metoprolol and propranolol.

Class II drugs are the workhorse of arrhythmia management because they are effective, generally safe, and have good evidence in atrial fibrillation, supraventricular tachycardia, ventricular tachycardia, and arrhythmias of ischaemia or thyrotoxicosis.

Side effects are covered in Hypertension and Heart Failure: bronchospasm (avoid in severe asthma), bradycardia, fatigue, cold extremities, masking of hypoglycaemia, and erectile dysfunction.

Class III: Potassium Channel Blockers

Class III drugs block potassium channels involved in repolarisation, prolonging the action potential and the refractory period. The two main UK drugs are amiodarone and sotalol.

Amiodarone is the most effective single antiarrhythmic, with activity across all four Vaughan-Williams classes. It is used in atrial fibrillation, atrial flutter, ventricular tachycardia and ventricular fibrillation, and as part of the Advanced Life Support algorithm for shockable rhythms. It can be given orally or intravenously. The trade-off is its remarkable side-effect profile, which is worth committing to memory:

• Pulmonary fibrosis: potentially fatal; baseline and routine pulmonary monitoring needed.
• Hepatic injury: LFT monitoring required.
• Thyroid disease: both hyperthyroidism and hypothyroidism (amiodarone is iodine-rich and blocks T₄ to T₃ conversion). Thyroid function monitoring required.
• Photosensitivity and slate-grey skin discolouration.
• Corneal microdeposits, occasionally optic neuropathy.
• Peripheral neuropathy.
• QT prolongation: risk of torsades de pointes (less than other class III drugs because of the rate-limiting effect).
• Drug interactions: potent inhibitor of multiple CYP enzymes; raises levels of warfarin, digoxin and statins among others.

Amiodarone has an enormous volume of distribution and a half-life measured in weeks; effects (and side effects) persist long after stopping.

Sotalol combines class III action with non-selective beta-blockade. Used for paroxysmal atrial fibrillation and some ventricular arrhythmias. Risk of torsades de pointes from QT prolongation is higher than with amiodarone.

Class IV: Calcium Channel Blockers

The non-dihydropyridine calcium channel blockers verapamil and diltiazem block L-type calcium channels in the AV node, slowing conduction and prolonging the refractory period. Their main use in arrhythmia is rate control in atrial fibrillation, atrial flutter, and termination of AV-nodal re-entrant supraventricular tachycardia.

The same drug class is covered for hypertension in Hypertension and Heart Failure. Two prescribing rules:

• Verapamil and diltiazem must never be combined with a beta-blocker: the additive AV nodal blockade can cause complete heart block.
• Both verapamil and diltiazem are contraindicated in heart failure with reduced ejection fraction because of their negative inotropy.

Drugs Outside the Vaughan-Williams Classification

Adenosine

Adenosine is given as a rapid intravenous bolus into a large vein (typically the antecubital fossa). It binds A₁ receptors at the SA and AV nodes, opens potassium channels, and produces transient AV nodal block.

The half-life is under 10 seconds: the briefest of any drug in the formulary, so its effects last only a few seconds. Adenosine has two main uses:

• Termination of AV-nodal re-entrant supraventricular tachycardia (SVT). The drug "breaks" the re-entrant circuit by transiently blocking the AV node.
• Diagnostic unmasking of underlying atrial activity when the rhythm is unclear (e.g. distinguishing atrial flutter from SVT).

The patient should be warned about the brief but unpleasant feeling of impending doom and chest tightness during administration. It is contraindicated in severe asthma (can cause bronchospasm).

Digoxin

Digoxin is a cardiac glycoside derived from foxglove (Digitalis). It inhibits the Na⁺/K⁺ ATPase, which secondarily increases intracellular calcium and produces a positive inotropic effect, and enhances vagal tone, which slows AV nodal conduction.

It is now used principally for rate control in atrial fibrillation, especially in patients who are sedentary or have heart failure, where its lack of negative inotropy is helpful. It is not effective for exercise-induced rate control, because vagal tone falls during exercise.

Digoxin has a narrow therapeutic index, a long half-life (around 40 hours, longer in renal impairment), and a high volume of distribution (around 500 L), so a loading dose is required. Toxicity ("digitalis toxicity") is the classic presentation worth knowing:

• Cardiac: almost any arrhythmia, classically bradycardia with ventricular ectopy or AV block.
• Gastrointestinal: nausea, vomiting, anorexia.
• Visual: the famous "yellow-green" colour vision (xanthopsia), thought to have influenced Vincent van Gogh's later paintings.
• Neurological: confusion, fatigue.

Risk factors for toxicity include renal impairment (digoxin is renally cleared), hypokalaemia (potassium and digoxin compete for the Na⁺/K⁺ ATPase: low potassium amplifies digoxin effects), and drug interactions. Amiodarone and verapamil raise digoxin levels directly via P-glycoprotein inhibition; diuretics increase the risk of toxicity indirectly by causing hypokalaemia and hypomagnesaemia, even though serum digoxin itself is unchanged. Severe toxicity is treated with digoxin-specific Fab antibody fragments (DigiFab).

Atropine

Atropine is a competitive antagonist at muscarinic acetylcholine receptors. By blocking vagal influence on the SA and AV nodes, it speeds heart rate and AV conduction. The standard dose is 500 micrograms intravenously, repeated up to a maximum of 3 mg, for symptomatic bradycardia (Resuscitation Council UK guidance). Side effects are predictable from anticholinergic action: dry mouth, blurred vision, urinary retention, constipation and confusion.

Ivabradine

Ivabradine selectively blocks the I_f ("funny") current at the SA node, slowing the heart rate without affecting blood pressure or contractility. It is used in:

• Chronic stable angina with intolerance to beta-blockers.
• HFrEF in patients in sinus rhythm with a heart rate above 75 bpm despite optimal beta-blockade.

Contraindicated in pregnancy; can cause visual phosphenes (luminous phenomena, due to a related I_h current in the retina).

Magnesium

Intravenous magnesium sulfate is the first-line treatment for torsades de pointes regardless of serum magnesium level. It is also given as part of asthma management and pre-eclampsia/eclampsia.

Pharmacological Management of Common Arrhythmias

Atrial Fibrillation

Atrial fibrillation (AF) is the most common sustained arrhythmia in the UK. The clinical questions in any patient with AF are:

1. Are they haemodynamically stable? If unstable (chest pain, syncope, heart failure), DC cardioversion is the priority.
2. Rate or rhythm control?
3. Anticoagulation: almost always yes for non-valvular AF unless CHA₂DS₂-VASc is very low. Covered in Antiplatelets, Anticoagulants and Thrombolysis.

Rate control is the default for most patients, particularly those over 65 with persistent AF. NICE NG196 offers either of the following as initial monotherapy:

• Beta-blocker (bisoprolol or atenolol).
• Rate-limiting calcium channel blocker (verapamil or diltiazem): not in HFrEF.

Digoxin is reserved for sedentary patients with non-paroxysmal AF, and as add-on therapy when beta-blocker (or rate-limiting CCB) monotherapy is insufficient. It is preferred in coexisting heart failure, where its lack of negative inotropy is helpful.

Rhythm control is preferred in younger patients, paroxysmal AF, AF with reversible cause, or when symptoms persist despite rate control:

• Flecainide: pill-in-the-pocket strategy for paroxysmal AF without structural heart disease.
• Amiodarone, for persistent AF, particularly with structural heart disease where flecainide is contraindicated.
• Sotalol: alternative.
• DC cardioversion, for first-presentation AF in younger patients, or where pharmacological cardioversion has failed.

Supraventricular Tachycardia

For paroxysmal SVT (typically AV-nodal re-entrant tachycardia, AVNRT):

1. Vagal manoeuvres first: carotid sinus massage or the modified Valsalva manoeuvre.
2. Adenosine 6 mg intravenous bolus, then 12 mg if needed.
3. Verapamil or a beta-blocker if adenosine is contraindicated.
4. DC cardioversion if unstable.

For long-term prevention: a beta-blocker, verapamil, or definitive treatment with catheter ablation.

Ventricular Tachycardia and Ventricular Fibrillation

Pulseless VT and VF are shockable rhythms in cardiac arrest; the Resuscitation Council Advanced Life Support algorithm uses amiodarone 300 mg IV after the third unsuccessful shock, with a further 150 mg considered after the fifth.

Stable VT with a pulse: amiodarone is first-line; lidocaine is an alternative.

Long-term: implantable cardioverter-defibrillator (ICD) for patients at high risk of recurrence.

Torsades de Pointes

Torsades de pointes ("twisting of the points") is a polymorphic ventricular tachycardia associated with QT prolongation. The standard treatment is intravenous magnesium sulfate, regardless of serum magnesium level. Any QT-prolonging drug must be stopped, and electrolyte abnormalities (hypokalaemia, hypomagnesaemia) corrected.

Symptomatic Bradycardia

Symptomatic bradycardia or AV block is treated with intravenous atropine 500 micrograms, repeated to a maximum of 3 mg. If atropine is ineffective, second-line options include intravenous adrenaline (epinephrine) infusion, isoprenaline, or transcutaneous pacing. Reversible causes (e.g. drug-induced bradycardia from beta-blockers, calcium channel blockers or digoxin) are treated specifically.

Summary

• The cardiac action potential has a fast form (working myocardium, sodium-driven phase 0) and a slow form (pacemaker tissue, calcium-driven phase 0 with funny-current automaticity).
• The Vaughan-Williams classification: I sodium channel blockers, II beta-blockers, III potassium channel blockers, IV calcium channel blockers. Memory aid: "Some Block Potassium Channels".
• Important unclassified drugs are adenosine (SVT), digoxin (rate control in AF), atropine (bradycardia), ivabradine (selective heart rate reduction), and magnesium (torsades).
• Atrial fibrillation management asks: stable or unstable? rate or rhythm? anticoagulation? Rate control with a beta-blocker, calcium channel blocker or digoxin is the default for most patients.
• SVT: vagal manoeuvres → adenosine.
• VT/VF: amiodarone in cardiac arrest; ICD for high-risk patients.
• Torsades: IV magnesium sulfate.
• Bradycardia: IV atropine, then pacing.
• Amiodarone's side-effect profile (lung, liver, thyroid, skin, eye, neuropathy) is high-yield for exams.

Drug Summary Table

Vaughan-Williams classification + the drugs outside it.

Reviewed by: Dr. Marcus Judge

Quiz

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