Management of Arrhythmias, Part II: Ventricular Arrhythmias

US Pharm. 2006;7:HS-23-HS-28.

Ventricular arrhythmias are disturbances in cardiac impulse generation or conduction that occur below the level of the bundle of His, which separates the atrial and ventricular tissues. These dysrhythmias include premature ventricular contractions (PVCs), ventricular tachycardias (VTs), ventricular fibrillation (VF), and sudden cardiac death (SCD). The rhythm disorders can be benign or lethal and occur more often in patients with structural heart disease.

Ventricular Arrhythmias
Premature Ventricular Contractions: PVCs are also known as ventricular premature beats and are characterized as abnormal, wide QRS complexes that occur prior to normal ventricular depolarization. PVCs are caused by ectopic ventricular pacemakers and usually last longer than 0.12 seconds.^1,2 PVCs may be seen in patients with or without structural heart disease. Several studies have shown that PVCs are present in about 30% of healthy people between the ages of 20 and 59 and in approximately 70% to 100% of those older than 60.³ In addition, according to the Atherosclerosis Risk in Communities study, PVCs are more common in men, African-Americans, and those with heart disease.⁴

In general, ventricular arrhythmias (including PVCs) are linked to many cardiac and noncardiac causes. Common cardiac conditions that may predispose patients to these arrhythmias include ischemic heart disease, heart failure/cardiomyopathy, and valvular disease. Noncardiac causes of ventricular arrhythmias include stimulants, such as caffeine and cocaine, electrolyte disturbances, acidosis, and drugs such as antipsychotics, tricyclic antidepressants, and antiarrhythmics.² Patients with PVCs may be asymptomatic or may experience palpitations, angina, hypotension, or worsening heart failure.¹

Treatment for PVCs is based on the presence of structural heart disease and symptoms. In patients with no evidence of heart disease, PVCs are generally not associated with an increased risk of mortality.¹ The frequency of these palpitations may be diminished by reducing or eliminating smoking, excessive caffeine consumption, alcohol intake, and use of drugs such as amphetamines. In addition, any electrolyte abnormalities, such as hypokalemia and hypomagnesemia, should be corrected.³ If otherwise healthy patients present with multiple PVCs and have severe symptoms, beta-blockers are the treatment of choice. Other options include amiodarone, flecainide, and radiofrequency ablation. ²

The results of the Cardiac Arrhythmia Suppression Trial (CAST) and CAST II are responsible for dramatically changing treatment strategies for patients with heart disease who experience PVCs. CAST's objective was to determine whether antiarrhythmic drugs would reduce the risk of cardiac arrest and total mortality for post-MI patients with asymptomatic PVCs. The study was terminated prematurely due to the higher total mortality and increased rates of death from arrhythmia and cardiac arrest with flecainide and encainide. CAST II showed that moricizine was also associated with an increased mortality in the same patient population. Thus, patients with structural heart disease and asymptomatic PVCs should not receive drug treatment, and those with symptoms should be treated with beta-blockers, which have been shown to decrease mortality in post-MI patients.¹ Use of sotalol, which has beta-blocking properties, was shown to reduce overall mortality post-MI; however, the Survival With Oral D-Sotalol trial showed that d-sotalol (an isomer with no beta-blocking properties) increased mortality.⁵ Amiodarone reduced mortality in post-MI patients with frequent PVCs in the Canadian Amiodarone Myocardial Infarction Arrhythmia Trial but had no mortality benefit in post-MI patients who had left ventricular dysfunction in the European Myocardial Infarct Amiodarone Trial. Amiodarone is a reasonable second-line therapy for patients with heart disease experiencing symptomatic PVCs when beta-blockers are ineffective or not tolerated.⁵

Nonsustained Ventricular Tachycardia: VT is defined as three or more PVCs at a rate greater than 100 bpm and can be further classified as nonsustained VT (NSVT) or sustained VT depending on the duration of the dysrhythmia. NSVT usually spontaneously terminates within 30 seconds and is not associated with hemodynamic instability. The severity of symptoms seen with VT depends on the duration of the arrhythmia, the ventricular rate, and the degree of the patient's heart disease. Patients who have NSVT, especially those without heart disease, are often asymptomatic or have mild symptoms, such as palpitations, dizziness, and syncope.¹

As with PVCs, treatment options for NSVT depend on the presence of structural heart disease (Table 1 ) In addition, treatment is based on the patient's left ventricular function. Patients without structural heart disease do not require treatment unless they are symptomatic. Beta-blockers are the preferred therapy in this instance. For post-MI patients experiencing NSVT, treatment is based on left ventricular ejection fraction (LVEF). Post-MI patients with LVEF greater than 40% and NSVT should receive a beta-blocker, regardless of symptoms. Patients with LVEF less than 40% and NSVT should undergo electrophysiologic (EP) testing to determine if the dysrhythmia is inducible. An implantable cardioverter defibrillator (ICD) should be used to treat inducible VT, and a beta-blocker or amiodarone should be used to treat noninducible VT.¹

Sustained Ventricular Tachycardia: Sustained VT can be classified as monomorphic or polymorphic, depending on the consistency of the QRS complexes on electrocardiogram. Torsades de pointes is a polymorphic VT that is associated with a prolonged QTc interval (Table 2). Both types of VT may be caused by acute MI, severe electrolyte abnormalities, hypoxemia, or drugs.⁶ Patients with sustained VT are usually symptomatic, and the arrhythmia can deteriorate into hemodynamic instability with severe hypotension, angina, and/or syncope. If VT goes untreated, it can deteriorate into VF and possibly cause death.¹ Treatment (Table 3) for any hemodynamically unstable VT is direct current cardioversion (DCC), which decreases the risk of VF.⁵ In addition, all patients with sustained VT should receive replacement electrolytes, if needed. Drug treatment for sustained monomorphic VT is based on the patient's left ventricular function. For patients who have an LVEF greater than 40%, the preferred antiarrhythmic is intravenous (IV) procainamide, although lidocaine or amiodarone is an acceptable alternative. ⁷ For patients with left ventricular dysfunction (LVEF <40%), amiodarone and lidocaine are the preferred agents because neither of these drugs acts as a negative inotrope. When treating torsades, it is important to discontinue any drug that may cause a prolonged QTc interval (Table 2). IV magnesium sulfate is usually considered the drug of choice for treatment of torsades, regardless of the patient's magnesium level. Since torsades may be caused or worsened by bradycardia, therapies that increase the heart rate may be effective for conversion to normal sinus rhythm. These treatments include insertion of a temporary transvenous pacemaker for overdrive pacing and isoproterenol. Finally, lidocaine or phenytoin may be effective for termination of torsades.⁷

Pulseless Ventricular Tachycardia/Ventricular Fibrillation

VF is defined as the absence of any organized electrical cardiac activity. As a result of total ventricular chaos, there is a loss of cardiac output, blood pressure, and pulse.¹ If resuscitation efforts are not made within five to seven minutes, death is inevitable.⁸ Indeed, most cases of SCD result from VF or VT.⁹ VF and sustained VT without a pulse can be successfully treated only with DCC, and patients with these dysrhythmias should be managed according to the current advanced cardiovascular life support (ACLS) guidelines published by the American Heart Association (AHA; Table 4) ¹⁰ The ACLS guidelines for pulseless VT and VF recommend using up to three shocks with increasing energy (200 joules, 200 to 300 joules, 360 joules) for initial treatment of these arrhythmias. If the dysrhythmia is persistent or recurrent, the next option is to administer epinephrine 1 mg IV push every three to five minutes or vasopressin 40 units IV push. The drug should be followed by one 360-joule shock. If epinephrine or vasopressin with a subsequent shock is unsuccessful, an additional antiarrhythmic agent should be given, again followed by DCC. Amiodarone 300-mg IV (or a 5-mg/kg) bolus is probably the preferred drug for refractory VF, as the results of the Resuscitation of Refractory Sustained Ventricular Tachyarrhythmias (ARREST) and the Amiodarone versus Lidocaine in Prehospital Ventricular Fibrillation Evaluation (ALIVE) studies showed that amiodarone was more effective than placebo (ARREST) or lidocaine (ALIVE) in survival to hospital admission. ^6,11,12 Other antiarrhythmic choices include lidocaine, magnesium, and procainamide. If a drug is successful in resuscitating the patient, it should be continued until the patient is stable.⁶

Sudden Cardiac Death
SCD is defined as death from a cardiac cause within one hour of onset of clinical symptoms.¹ Approximately 80% of patients with SCD have a history of coronary heart disease.⁹ As previously mentioned, SCD usually results from VF or VT. In a study of out-of-hospital arrests, 62% were due to VF, 7% to VT, and 31% to asystole or other arrhythmias. Prevention is the most effective "treatment" of SCD, as it is the single leading cause of death in the United States; less than 5% of patients are successfully resuscitated.¹³

Prevention of SCD from cardiac causes is divided into two basic strategies: primary prevention and secondary prevention. The focus of primary prevention is treating patients who are post-MI or have cardiac disease, in order to prevent a life-threatening arrhythmia. The goal of secondary prevention is to prevent the recurrence of a fatal arrhythmia.¹⁴ The primary prevention studies Multicenter Automatic Defibrillator Implantation Trial (MADIT), Multicenter Unsustained Tachycardia Trial (MUSTT), and MADIT II showed the survival benefit of a prophylactic ICD in patients with both cardiac disease and left ventricular dysfunction. With the exception of the EP-guided antiarrhythmic agents used in MUSTT, the antiarrhythmic drugs in these studies were not generally associated with a mortality benefit.^1,15 Mortality benefit has been shown in this patient population with several other drugs, including beta-blockers, aspirin, statins, angiotensin-converting enzyme inhibitors, and spironolactone. ¹⁵ Secondary prevention studies, such as the Antiarrhythmics Versus Implantable Defibrillators, the Canadian Implantable Defibrillator Study, and Cardiac Arrest Study Hamburg, have shown the survival benefit of ICDs in patients who have already experienced cardiac arrest. A meta-analysis of these studies showed a 28% relative reduction in the risk of overall death and a 50% relative reduction in the risk of death from arrhythmia in patients receiving an ICD compared to those receiving amiodarone.¹ Based on the results of the secondary prevention trials, ICDs are indicated for first-line treatment in patients with a history of VT or VF. Amiodarone or sotalol can be added to the therapy of patients who experience frequent ICD discharges.¹

Role of the Pharmacist in Ventricular Arrhythmias

Pharmacists have an important role in the treatment of patients with cardiac arrhythmias. Antiarrhythmic medications are associated with many adverse effects, as well as numerous drug interactions. Pharmacists must closely monitor patients to ensure that they are receiving effective therapy with minimal side effects. Patients should receive extensive education to recognize symptoms associated with toxic effects of individual antiarrhythmics or a combination of these agents. In addition, patients should check with their pharmacist or physician before selecting any OTC medication and should avoid alternative treatment or herbal supplementation.

Some pharmacists are ACLS certified and can assist patients who require treatment for life-threatening arrhythmias. Pharmacists should monitor patients at risk for proarrhythmia for electrolyte disturbances and any sign or symptom of arrhythmia. Pharmacists in all practice settings should be familiar with automated external defibrillators, which are available in many public places. The AHA provides training to health care workers and family members in using these lifesaving devices.

Conclusion

Management of cardiac arrhythmias has changed drastically in the last decade due to the success of procedures such as radiofrequency ablation and surgery and the development of the ICD. Antiarrhythmic drug therapy has many limitations, including adverse effects, drug interactions, and proarrhythmic potential. However, millions of Americans suffer from arrhythmias, and many patients rely on these drugs to control symptoms and increase quality of life. It is important for pharmacists to have an understanding of arrhythmias as well as of prevention and treatment of these disorders.

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