How do I pick the right anti-arrhythmic? (Proceedings)

Introduction:

In veterinary medicine pharmacologic treatment to control or convert arrhythmias is the most common method employed. Drugs chosen are often limited to clinicians' experience and comfort level and drug availability. Appropriate pharmacologic management of patients with cardiac rhythm disturbances is often successful but these drugs are not without downsides some of which are lethal in nature. These problems include (but are not limited to) the narrow toxic to therapeutic ratio of some drugs. Many of these agents have negative inotropic effects that limit there use in patients with systolic dysfunction; inhibition of normal sinus function, pro-arrhythmic effects, arrhythmias are or become refractory to appropriate drug therapies. When pharmacologic therapy fails or is inappropriate for a given case, clinicians should be aware of other options that clients may avail their animals to.

Arrhythmogenesis and Pharmacologic therapy review:

As a matter of review arrhythmias can be caused by abnormalities of impulse initiation, impulse conduction or both. Conduction abnormalities commonly result in conduction delays and blocks with resultant bradycardia but can also become an important contributor to the formation of tachyarrhythmias. Abnormalities of impulse formation can produce both bradyarrhythmias and tachyarrhythmias. General these mechanisms result in abnormal automaticity (including enhanced or depressed normal automaticity), triggered activity or reentry phenomena (considered the most common cause).

Disorders of impulse conduction: Conduction abnormalities may lead to bradyarrhythmias secondary to conduction delays or blocks within the specialized conduction system. Such failures within this system result in sinus node exit block, second or third-degree atrioventricular (AV) block and bundle branch block. Conduction blocks can occur in myocardial tissues damaged by ischemia, infarction, stretch, or drug toxicity. High vagal tone can result in slowed SA nodal discharge or block at the AV node. Lack of impulse conduction may also lead to tachyarrhythmias as conduction through abnormal or diseased cardiac tissue may behave very differently than through normal cardiac tissue that could result in a condition termed reentry. Normally in sinus rhythm the atria and ventricles are activated in a specific and relatively constant pattern where each impulse dies as the wave-front reaches its limits. If re-entrant activation occurs, the propagating impulse does not die out in the usual way and persists to re-excite the chambers of the heart in a cyclic pattern after the end of the refractory period. There are two necessary conditions for classic re-entry to occur; (1) unidirectional conduction block of the impulse, and (2) slow conduction (relative to refractoriness of the surrounding cardiac cells). Re-entry is thought to be the most common cause of tachyarrhythmias and can exist as functional re-entry or anatomical re-entry.

Disorders of impulse formation encompass enhanced or depressed impulse formation by normal pacemaker cells and abnormal impulse formation by cells that are normally not automatic in nature. Depression in normal automaticity results in a decrease in the discharge rate of an automatic site (often from increased vagal tone or diseased automatic cells) is manifested as bradyarrhythmias. In contrast enhanced automaticity results in tachyarrhythmias. Sinus tachycardia as the best example is caused enhanced output from the sinus node. Other automatic tissues (subsidiary pacemakers) may be enhanced and usurp control of the heart's rhythm thus presenting as premature complexes.

Abnormal automaticity thought to be an important cause of atrial and ventricular arrhythmias originating from working myocardial cells that lack automaticity under normal circumstances. It can develop after damage to the cardiac tissue secondary to ischemia, stretch, or drug toxicity. Triggered Activity occurs only if the pacemaker has previously been driven by an appropriate action potential or series of action potentials. Thus in contrast to automatic rhythms, triggered rhythms occur only after an initiating beat that produces depolarizing afterpotentials. These afterpotentials are classified into two subgroups:

Early Afterdepolarizations (EADs) occur during either phase 2 or phase 3 of the normal action potential. These interrupt repolarization and the action potential oscillates to a threshold and depolarizes the cell. In general, conditions that prolong the action potential duration will tend to increase the amplitude of EADs and thus the likelihood of triggering from the plateau leve and tend to occur in conditions that slow heart rate/conduction significantly and can be abolished by very short action potential cycles.

Delayed Afterdepolarizations (DADs) occur after full repolarization of the action potential there are oscillations in the resting membrane potential that reach threshold and cause depolarization. They have been found to be associated with transient inward currents caused by oscillatory release of calcium from the sarcoplasmic reticulum in diastole. The amplitude of DADs and the incidence of triggered activity is directly proportional to the rate and duration of the train of action potentials used to elicit them. Thus these are typically associated with rapid heart rates. This is thought to be the mechanism associated with digoxin toxicity.

While often time one of these mechanisms dominates the perpetuation of an arrhythmia, multiple mechanisms may be involved. Drug therapy is often aimed specifically at interruption of these mechanisms by either decreasing abnormal automaticity or prolonging refractoriness. A simple review of these drugs based on the Vaughn-Williams classification and there categories of action is shown in Table 1. While one cannot usually decipher a specific mechanism based on surface ECG an understanding of the mechanism that cause arrhythmias may help one to understand how the anti-arrhythmics function to break the pathological rhythms.

Table 1.

So what are my other options? That depends on what you are treating.

Pacemaker Therapy:

Pacemakers are devices that deliver electrical stimuli through electrodes that are in contact with the heart muscle to produce artificially triggered electrical depolarization. Primary indications for pacemaker placement in veterinary medicine are symptomatic bradyarrhythmias and conduction disturbances that are not responsive to medical therapy. Some of the more common arrhythmias treated with artificial pacing include symptomatic sick sinus syndrome, high-grade second degree and third (complete) atrioventricular blocks, as well as persistent atrial standstill. Pacemaker therapy may also be used in combination with other therapies to control tachyarrhythmias (to be discussed in a later section)

Direct Current Cardioversion:

This technique is also called defibrillation. With this technology a high-energy impulse of short duration is delivered across the heart. Successful DC cardioversion results when a critical myocardial mass is depolarized by a DC shock and a cardiac pacemaker such as the SA node recommences its control of the hearts rhythms. This technique has been employed for treatment of conversion of atrial fibrillation back to normal sinus rhythm, supraventricular tachycardias, ventricular tachycardia or fibrillation.

Radiofrequency Catheter Ablation:

Radiofrequency catheter ablation (RCA) is also available for veterinary patients. Its use in veterinary medicine unlike human medicine has be primarily for atrial tachycardia. Electrophysiologic (EP) testing is generally performed to definitively diagnose the arrhythmia in some cases and but mostly to ascertain the location of the source of the arrhythmia. The goal of RFA is to irreversibly damage a portion of the cardiac tissue involved in a fixed reentry circuit (most common use in veterinary patients) or automatic focus.

So How Do I Choose?

At right, there is a basic algorithm that we suggest for treatment of arrhythmias. In the seminar we will discuss specific arrhythmias and follow up to chronic therapy.

Algorithm

Chronic therapeutic decision:

Once the clinician has decided on chronic therapy appropriate monitoring of therapeutic should be performed. We recommend Holter monitoring of patients to assess quality of control of the rhythm. Ideally animals should be allowed to return to there home environment when performing this test to reduce stress levels and introducing other variants that may perpetuate arrhythmias.

Conclusions:

Understanding the mechanisms that underlie most abnormal rhythms helps one to understand how each class of anti arrhythmics can work to break abnormal heart rhythms. While pharmacological management of cardiac arrhythmias will most likely continue as the mainstay of veterinary patients, clinicians need to be aware of alternative and sometimes more definitive treatment options for their patients. Also one must still remember that it may take combinations of these therapeutic modalities to best treat our patients.

Reference:

Available upon request

Keywords: Arrhythmogenesis. Cardioversion, pacemaker therapy, radiofrequency ablation