Cardiac arrhythmias are the most common cause of death in patients with a myocardial infarction or terminal heart failure. They are also the most serious manifestation of digitalis toxicity and are often associated with anesthetic procedures, hyperthyroidism, and electrolyte disorders. The drugs used for arrhythmias fall into five major groups or classes, but most have very low therapeutic indices and when feasible, nondrug therapies (cardioversion, pacemakers, ablation, implanted defibrillators) are used.
Normal electrical cardiac function (normal sinus rhythm, NSR) is dependent on generation of an impulse in the normal sinoatrial (SA) node pacemaker and its conduction through the atrial muscle, through the atrioventricular (AV) node, through the Purkinje conduction system, to the ventricular muscle (Figure 14–1) where it is finally extinguished after activating all the myocytes. A new impulse must arise in the SA node for the next conducted action potential. Normal pacemaking and conduction require normal action potentials (dependent on sodium, calcium, and potassium channel activity) under appropriate autonomic control. Arrhythmias (also called dysrhythmias) are therefore defined by exclusion, that is, an arrhythmia is any cardiac rhythm that is not normal sinus rhythm.
Schematic representation of the heart and normal cardiac electrical activity (intracellular recordings from areas indicated and ECG). The ECG is the body surface manifestation of the depolarization and repolarization waves of the heart. The P wave is generated by atrial depolarization, the QRS by ventricular muscle depolarization, and the T wave by ventricular repolarization. The PR interval is a measure of conduction time from atrium to ventricle through the atrioventricular (AV) node, and the QRS duration indicates the time required for all of the ventricular cells to be activated (ie, the intraventricular conduction time). The QT interval reflects the duration of the ventricular action potential. SA, sinoatrial. (Reproduced, with permission, from Katzung BG, editor: Basic & Clinical Pharmacology, 12th ed. McGraw-Hill, 2012: Fig. 14–1.)
Abnormal automaticity and abnormal conduction are the 2 major mechanisms for arrhythmias. Abnormalities of conduction include reentrant conduction and less commonly, complete block. A few of the clinically important arrhythmias are atrial flutter, atrial fibrillation (AFib), atrioventricular nodal reentry (a common type of supraventricular tachycardia [SVT]), premature ventricular beats (PVBs), ventricular tachycardia (VT), and ventricular fibrillation (VF). Examples of electrocardiographic (ECG) recordings of normal sinus rhythm and some of these common arrhythmias are shown in Figure 14–2. Torsades de pointes is a ventricular arrhythmia of great pharmacologic importance because it is often induced by antiarrhythmic and other drugs that change the shape of the action potential and prolong the QT interval. It has the ECG morphology of a polymorphic ventricular tachycardia, often displaying waxing and waning QRS amplitude. Torsades is also associated with long QT syndrome, a heritable abnormal prolongation of the QT ...