Chapter 25 Cardiac arrhythmia
Some physiology and pathophysiology
There are broadly two types of cardiac tissue.
Ionic movements into and out of cardiac cells
In the resting state the interior of the cell (conducting and contracting types) is electrically negative with respect to the exterior, owing to the disposition of ions (mainly sodium, potassium and calcium) across its membrane, i.e. it is polarised. The ionic changes of the action potential first result in a rapid redistribution of ions such that the potential alters to positive within the cell (depolarisation); subsequent and slower flows of ions then restore the resting potential (repolarisation). These ionic movements separate into phases, which are briefly described here and in Figure 25.1, as they help to explain the actions of antiarrhythmic drugs.1
Classification of antiarrhythmic drugs
The classification still used partially relates to the phases of the cardiac cycle depicted in Figure 25.1.
Phase 3 is a second period of rapid repolarisation during which potassium ions move out of the cell.
Most cardiac arrhythmias are due to either:
• slowed conduction in part of the system leading to the formation of re-entry circuits (more than 90% of tachycardias), or
• altered rate of spontaneous discharge in conducting tissue. Some ectopic pacemakers appear to depend on adrenergic drive.
Classification of drugs
The Vaughan–Williams2 classification of antiarrhythmic drugs is still commonly used despite its many peculiarities, and on occasion provides a useful shorthand for referring to particular groups or actions of drugs.
Class I: sodium channel blockade
1A. lengthen action potential duration and refractoriness (adjunctive class III action), e.g. quinidine, disopyramide, procainamide
1B. shorten action potential duration and refractoriness, e.g. lidocaine and mexiletine
1C. have negligible effect on action potential duration and refractoriness, e.g. flecainide, propafenone.
Principal drugs by class
For further data see Table 25.1.
Class 1A (sodium channel blockade with lengthened refractoriness)
Quinidine
Quinidine is considered the prototype antiarrhythmic drug,3 although it is now used quite rarely and indeed is not available in some jurisdictions. It has a newly identified use that is unique in that it appears to be effective in reducing the risks of sudden cardiac death in those with Brugada syndrome.4 In addition to its class IA activity, quinidine slightly enhances contractility of the myocardium (positive inotropic effect) and reduces vagus nerve activity on the heart (antimuscarinic effect).
Adverse reactions
Quinidine must not be used alone to treat atrial fibrillation or flutter as its antimuscarinic action enhances AV conduction and the heart rate may accelerate. Other cardiac effects include serious ventricular tachyarrhythmias associated with electrocardiographic QT prolongation, i.e. torsade de pointes (Fig. 25.2), the cause of ‘quinidine syncope’. Non-cardiac effects, called ‘cinchonism’, include diarrhoea and other gastrointestinal symptoms, rashes, thromobocytopenia and fever, and these have substantially limited its use.
Class IB (sodium channel blockade with shortened refractoriness)
Class IC (sodium channel blockade with minimal effect on refractoriness)
Flecainide
One common indication – indeed where it is the drug of choice – is atrioventricular (AV) re-entrant tachycardia, such as AV nodal tachycardia or in the tachycardias associated with the WPW syndrome or similar conditions with anomalous pathways. This should be as a prelude to definitive treatment with radiofrequency ablation, which is the overall treatment approach of choice. Flecainide is also very useful in patients with paroxysmal atrial fibrillation, used in conjunction with an agent that blocks the AV node to protect against rapid conduction to the ventricle. Following the salutary findings of the CAST study,5 flecainide is now restricted to patients without evidence of coronary or structural heart disease. Indeed before it is used an echocardiogram is essential, and in patients at potential risk of coronary artery disease an exercise test or an alternative test of ischaemia is often conducted.
Class II (catecholamine blockade)
β-Adrenoceptor antagonists
• The rate of automatic firing of the SA node is accelerated by β-adrenoceptor activation and this effect is abolished by β-blockers. Some ectopic pacemakers appear to be dependent on adrenergic drive.
• β-blockers prolong the refractoriness of the AV node, which may prevent re-entrant tachycardias that are dependent on the AV node for their perpetuation.
• Many β-blocking drugs (propranolol, oxprenolol, acebutolol, labetalol) also possess membrane stabilising (class I) properties. Sotalol also prolongs cardiac refractoriness (class III effect) but has no class I effects; it is often preferred when a β-blocker is indicated for arrhythmias, but should be used with care. Esmolol (below) is a short-acting β1-selective agent, whose sole use is in the treatment of arrhythmias. Its short duration and β1 selectivity make it an option for some patients with contraindications to other β-blocking drugs.
• β-Adrenoceptor antagonists are effective for a range of supraventricular arrhythmias, in particular those associated with exercise, emotion or hyperthyroidism. Sotalol finds use to suppress ventricular ectopic beats and ventricular tachycardia although care should be taken with careful monitoring of the QT interval whenever it is used.