An arrhythmia (also termed cardiac dysrhythmia) is described as an irregular heartbeat caused by aberrant electrical activity in the heart. There are multiple categories of arrhythmia, each of which can result in a heartbeat which is either too slow (bradycardia) or too fast (tachycardia). Atrial and ventricular fibrillation, which represent the most common cardiac arrhythmias, cause between 10 and 20% of all adult deaths in the Western world. The occurrence of atrial fibrillation is increased with age; it not only impacts cardiac function, but also enhances the risk of stroke, and can even aggravate heart failure.
A regular heartbeat is driven by varying stages of membrane depolarization and repolarization in single heart cells which propagate from the sinoatrial (SA) node to the atrium and the ventricle. There are two categories of action potentials: the slow response, evident in the SA and atrioventricular (AV) nodes, and the rapid response action potential, which transpires in cardiac muscle and Purkinje fibers. Action potentials allow fast alterations in heart rate. The contraction of the cardiac muscle happens in response to depolarization. Through the generation of action potentials, a way of depolarization is set off, and the SA node thus functions as a pacemaker, establishing the rate of contraction of the heart. Consequently, the dysfunction of the SA node can lead to an irregular heartbeat.
Figure 1. Action potentials in cardiac muscle cells
The process of normal cardiac action potential generation in cardiac muscle cells is presented in Figure 1. The effective refractory period (ERP) is a process that helps fortify the heart from arrhythmias by blocking the production of new action potentials during the propagation of one which already exists.
Antiarrhythmics
Antiarrhythmics, including quinidine can be utilized to extend the ERP, which prevents premature activation. Unfortunately, quinidine also extends the QT interval (Figure 2) and can also instigate Torsades de pointes (TdP; a category of ventricular tachycardia that can be transient or cause lethal ventricular fibrillation). As well as SA node dysfunction, arrhythmias may also happen as a consequence of abnormalities in the electrophysiology of heart cells or in cell-to-cell (impulse) propagation, which occurs through gap junctions. These allow the conduction of a wave of depolarization between cells.
Ion channels administer the conduction of coordinated electrical impulses, and therefore the development of arrhythmias has been linked to dysregulation of their activity. For instance, mutations in genes that encode the calcium CaV1.2 channel, the KV11.1 (hERG) potassium channel and the sodium NaV1.5 channel have been associated with long QT syndrome (LQTS). In LQTS, the QT interval is prolonged and repolarization is held up; this enhances the risk of Torsades de pointes. Cardiac ion channel blockade is the conventional action of antiarrhythmic drugs. Directly or indirectly modifying ion channel conductance alters the properties of cardiac action potentials and lowers atrial fibrillation.
Figure 2. ECG traces of arrhythmia. Arrhythmias can be detected by electrocardiography (ECG or EKG), which measures the electrical activity of the heart. A normal ECG trace will have a consistent, regular form, representing the different intervals involved in cardiac rhythm. This includes the QT interval, during which the left and right ventricles depolarize and repolarize. During ventricular fibrillation, a type of arrhythmia, the heart does not contract in an ordered fashion; the absence of normal heart rhythm is apparent when comparing ECG traces.
Antiarrhythmic Drug Treatment
As well as ionic imbalances, arrhythmogenic stimuli in the heart comprise thrombosis, metabolic substances (e.g. phospholipids and eicosanoids), atheromas, and coronary artery spasm (angina). Arrhythmias can also be caused by myocardial ischemia. Antiarrhythmic drug treatment is directed at the restoration of normal cardiac conduction and rhythm, and the prevention of more serious arrhythmias from transpiring. Vaughan Williams initiated one of the most broadly utilized classification schemes for antiarrhythmic drugs. The program distinguishes antiarrhythmic drugs into five classes (I-V), each of which corresponds to a distinct target.
Class I compounds comprise sodium channel blockers; class II comprise beta-blockers; class III comprises agents targeting potassium channels, and class IV agents block calcium channels. Class V comprises drugs that function via an unknown mechanism. These classes also include additional subclasses, which manifest somewhat divergent characteristics at divergent points of the cardiac action potential, and which might also influence the overall duration of the action potential.
For specific categories of arrhythmia, divergent agents can also be utilized: for instance, adenosine and verapamil can be utilized in the treatment of supraventricular tachycardia. The primary developments in arrhythmic therapy are represented by the usage of electronic devices such as artificial pacemakers and direct current cardioversion.
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