Dysrhythmias

Cardiac Cellular Electrophysiology

The term dysrhythmia denotes any abnormality in cardiac rhythm; it is often used interchangeably with the term arrhythmia . Understanding dysrhythmias begins with understanding the normal electrophysiologic function of cardiac cells. Electrophysiology depends on an intact resting membrane potential, largely the result of differential concentrations of Na ⁺ and K ⁺ on either side of the cell membrane, measuring approximately −90 mV in normal resting nonpacemaker cells. This gradient exists because of the Na ⁺ K ⁺ exchange pump and concentration-dependent flow of K ⁺ out of the cell. The influx of Ca ²⁺ through passive exchange with Na ²⁺ also allows for conduction and myofibril contraction ( Fig. 65.1 ).

In normal nonpacemaker cells, an electrical stimulus causes the membrane potential to become less negative, termed depolarization. When the membrane potential reaches −70 mV, specialized Na ²⁺ channels open, causing a rapid influx of positive charge into the cell. This so-called fast channel activity further decreases the membrane potential and is augmented at 30 to 40 mV by a second slow channel that allows Ca ²⁺ influx. When these channels close, the resting potential is restored by the sodium-potassium pump, an event termed repolarization ( Fig. 65.2 ).

In nonpacemaker cells, depolarization from a second electrical stimulus is not possible when the membrane potential remains more positive than −60 mV, called the effective refractory period ( Fig. 65.3 ). When the membrane potential reaches −60 to −70 mV, some fast channels are capable of responding but impulse propagation is not normal; this is known as the relative refractory period. At a membrane potential of −70 mV or less, fast channels are ready for activity (see Fig. 65.3 ).

Pacemaker cells differ from non–impulse-generating cells in that they can spontaneously depolarize via slow Na ⁺ influx. Dominant pacemaker cells are present in the sinoatrial (SA) node, but other pacemaker cells exist in the atrioventricular (AV) node, within the His-Purkinje system, and elsewhere. With a failure of normal pacemaking cells, or in the setting of other pathologic conditions such as metabolic derangement or myocardial ischemia, nonpacemaker cells undergo spontaneous depolarization.

Anatomy and Conduction

The SA node is an area of specialized impulse-generating tissue at the junction of the right atrium and the superior vena cava. Its blood supply is from the right coronary artery (RCA) in 55% of patients and left circumflex artery (LCA) in 45%. The normal SA node produces spontaneous depolarization faster than other pacemakers and is usually the dominant pacemaker. In healthy adults, the SA node typically maintains a rate of 60 to 90 beats/min. Hypothermia and vagal stimulation slow the sinus rate, whereas hyperthermia and sympathetic stimulation increase the rate. Low or absent parasympathetic tone—for example, with certain drugs or after heart transplantation—results in a faster sinus rate.

In the absence of normal SA node impulses, other myocardial tissues may assume the role of a pacemaker. The AV node has an intrinsic impulse-generating rate of 45 to 60 beats/min. Infranodal pacemakers within the His bundle, Purkinje system, and bundle branches maintain intrinsic rates ranging from 30 to 45 beats/min. Under pathologic conditions, other atrial and ventricular tissues may pace the heart at varying rates.

Impulses from the SA node are propagated through the atrial tissue to the AV node. Atrial depolarization is characterized by the P wave on the surface electrocardiogram (ECG; Fig. 65.4 ).

The AV node is an area of conduction tissue separating the atria and the ventricles, located in the posterior-inferior region of the interatrial septum. Its blood supply is from a branch of the RCA in 90% of patients (right dominant) and from the LCA in the remaining 10% (left dominant). Transmission of impulses within the AV node is slower than in other parts of the conducting system ( Table 65.1 ) because of a dependence on slow-channel ion influx for membrane depolarization. An accessory pathway refers to conduction tissue outside the AV node that forms an alternative, or bypass, tract between the atria and ventricles. The term preexcitation refers to early ventricular depolarization via an accessory pathway.

On the surface ECG, the time it takes to conduct an impulse through the atria to the ventricles is represented by the PR interval, normally ranging from 0.10 to 0.20 second (see Fig. 65.4 ). Impulses originating in lower atrial tissues or accessory pathways often have a shortened PR interval. PR prolongation is usually a result of nodal or supranodal conduction system disease.

After passing through the AV node, impulses propagate to the His bundle onto the three main bundle branch fascicles—the right bundle branch (RBB), left anterior-superior bundle (LASB), and left posterior-inferior bundle (LPIB). The RBB and LASB are typically supplied by the left anterior descending (LAD) artery, whereas the RCA or LCA may supply the LPIB. After conduction down the three main bundle branches, impulses are delivered to the Purkinje fibers, propagating impulses to myocardial tissues in a swift and orderly fashion, allowing for coordinated ventricular contraction. If an impulse arrives prematurely, it may be conducted abnormally (termed aberrant , associated with bundles that are relatively refractory) or blocked (if the bundles are entirely refractory).

On the ECG, the QRS complex represents ventricular depolarization (see Fig. 65.4 ), normally 0.09 second or less; 0.12 second or longer is abnormal. The T wave corresponds to ventricular repolarization and its duration depends, among other things, on the length of the cardiac cycle. The QT interval represents the total time of ventricular depolarization and repolarization and is altered by inherent physiologic abnormalities, metabolic changes, drugs, or structural changes. This interval is key to assess for QT prolongation in any patient with syncope or ventricular dysrhythmia, given the link to ventricular dysrhythmia recurrence.

Mechanisms of Dysrhythmia Formation

Enhanced automaticity refers to spontaneous depolarization in nonpacemaker cells or depolarization at an abnormally low threshold in pacemaker cells ( Fig. 65.5 ). Classic examples of enhanced automaticity include the idioventricular rhythms of severe hyperkalemia or myocardial ischemia and the atrial or junctional tachycardias (JTs) associated with digoxin toxicity.

Triggered activity refers to abnormal impulse(s) resulting from afterdepolarizations. Afterdepolarizations are fluctuations in membrane potential that occur as the resting potential is restored. These fluctuations may precipitate another depolarization just before the full resting potential is reached (early afterdepolarizations) or after full resting potential is reached (delayed afterdepolarizations). The classic dysrhythmia associated with early afterdepolarization is acquired torsades de pointes, which typically arises in the setting of a prolonged QT interval and a new metabolic or drug trigger. Delayed afterdepolarizations classically arise in the setting of rapid heart rates and intracellular Ca ²⁺ overload, as seen with digoxin toxicity or reperfusion therapy for acute myocardial infarction.

Reentry dysrhythmias arise from repetitive conduction of impulses through a self-sustaining circuit ( Fig. 65.6 ). To maintain a reentry circuit, one conduction pathway must have a longer refractory period than the other so that when an impulse exits one limb of the circuit, it may then reenter the other in retrograde fashion. The cycle is then repeated, creating self-sustaining dysrhythmia. Reentry mechanisms are responsible for most regular narrow-complex tachycardias and many ventricular tachycardias (VTs). Treatment is predicated on altering conduction in one or both limbs of the circuit.

Class IA Agents

Class IA agents slow conduction through the atria, AV node, and His-Purkinje system and suppress conduction in accessory pathways. As such, they slow both depolarization and repolarization. Class IA agents also exhibit anticholinergic and mild negative inotropic effects.

Class IB Agents

Class IB agents slow conduction and depolarization less than other class I agents, and they shorten repolarization rather than prolonging it. Class IB agents have little effect on accessory pathway conduction.

Class IC Agents

The class IC agents profoundly slow depolarization and conduction. More than any other class, these agents are associated with prodysrhythmia , the creation of a new dysrhythmia; this potential new dysrhythmic event also exists with class IA agents albeit much less than class IC. Class IC agents are approved for oral use in the United States.

Class II Agents

Class II agents—β-adrenergic blockers—suppress SA node automaticity and slow conduction through the AV node. Because of their effect on AV node conduction, class II agents are well suited to control the ventricular rate in patients with atrial tachydysrhythmias and can be useful to terminate AV nodal reentrant tachycardias (AVNRTs). In the setting of acute myocardial ischemia, beta blockers may lessen the frequency of ventricular dysrhythmias.

All beta blockers are active at β ₁ and β ₂ receptors ( Table 65.2 ) to varying degrees; those with more prominent β ₁ effects are called cardioselective. Relative contraindications to the use of beta blockers include advanced congestive heart failure and third-trimester pregnancy. Historically, beta blockers have been avoided in patients with asthma and chronic obstructive pulmonary disease. However, cardioselective beta blockers are not associated with an increased risk of asthma or chronic obstructive pulmonary disease (COPD) exacerbations. Beta blockers should not be used in patients with preexisting bradycardia or heart block beyond first-degree. Acute side effects of beta blockers include heart failure, excessive bradycardia, and hypotension. In rare cases, they may cause bronchospasm, but most instances are not clinically apparent. Intravenous (IV) beta blockers can trigger additive side effects when used in conjunction with calcium channel blockers, notably hypotension or bradycardia. Only two beta blockers are commonly used in emergency care of dysrhythmias.

Class III Agents

All class III agents prolong the refractory period primarily by blocking K ⁺ channels, with variable effects on the QT interval. In general, class III agents are alternatives to class I agents for the treatment of many ventricular and atrial dysrhythmias.