AUTHOR INFORMATION

Section 1 of 12

Authored by Sarah Stahmer, MD, Residency Director, Associate Professor, Department of Emergency Medicine, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School

Coauthored by Edwin Williams, MD, Consulting Staff, Department of Emergency Medicine, Einstein Hospital

Sarah Stahmer, MD, is a member of the following medical societies: Society for Academic Emergency Medicine

Edited by Assaad J Sayah, MD, Chief, Department of Emergency Medicine, Cambridge Health Alliance; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Eddy Lang, MDCM, CCFP (EM), CSPQ, Assistant Professor, Department of Family Medicine, McGill University; Consulting Staff, Department of Emergency Medicine, The Sir Mortimer B Davis-Jewish General Hospital; John Halamka, MD, Chief Information Officer, CareGroup Healthcare System, Assistant Professor of Medicine, Department of Emergency Medicine, Beth Israel Deaconess Medical Center; Assistant Professor of Medicine, Harvard Medical School; and Charles V Pollack, Jr, MD, MA, FACEP, Professor, Department of Emergency Medicine, University of Pennsylvania College of Medicine; Chairman, Department of Emergency Medicine, Pennsylvania Hospital

Author's Email:	Sarah Stahmer, MD
Editor's Email:	Assaad J Sayah, MD

eMedicine Journal, September 26 2005, VOLUME 6, Number 9

INTRODUCTION

Section 2 of 12

Background: Premature ventricular contraction (PVC) is caused by an ectopic cardiac pacemaker located in the ventricle. PVCs are characterized by premature and bizarrely shaped QRS complexes usually wider than 120 msec on with the width of the ECG. These complexes are not preceded by a P wave, and the T wave is usually large, and its direction is opposite the major deflection of the QRS.

The clinical significance of PVCs depends on their frequency, complexity, and hemodynamic response.

Pathophysiology: PVCs reflect activation of the ventricles from a site below the atrioventricular node (AVN). Suggested mechanisms for PVCs are reentry, triggered activity, and enhanced automaticity.

Reentry occurs when an area of 1-way block in the Purkinje fibers and a second area of slow conduction are present. This condition is frequently seen in patients with underlying heart disease that creates areas of differential conduction and recovery due to myocardial scarring or ischemia. During ventricular activation, the area of slow conduction activates the blocked part of the system after the rest of the ventricle has recovered, resulting in an extra beat. Reentry can produce single ectopic beats or can trigger paroxysmal tachycardia.

Triggered beats are considered to be due to after-depolarizations triggered by the preceding action potential. These are often seen in patients with ventricular arrhythmias due to digoxin toxicity and reperfusion therapy after myocardial infarction (MI).

Enhanced automaticity suggests an ectopic focus of pacemaker cells in the ventricle that has a subthreshold potential for firing. The basic rhythm of the heart raises these cells to threshold, which precipitates an ectopic beat. This process is the underlying mechanism for arrhythmias due to excess catecholamines and some electrolyte deficiencies, particularly hyperkalemia.

Factors that increase the risk of PVCs include male sex, advanced age, African American race, hypertension and underlying ischemic heart disease, a bundle branch block on 12-lead ECG, hypomagnesemia, and hypokalemia.

Frequency:

• In the US: PVCs are one of the most common arrhythmias and can occur in patients with or without heart disease. The prevalence of PVCs varies greatly, with estimates of less than 3% to more than 60% in asymptomatic individuals.

  Data from large, population-based studies indicate that the prevalence ranges from less than 3% for young white women without heart disease to almost 20% for older African American individuals with hypertension.

Mortality/Morbidity: The clinical significance of PVCs depends on the clinical context in which they occur.

• PVCs in young, healthy patients without underlying structural heart disease are usually not associated with any increased rate of mortality.

• PVCs in older patients, in particular those with underlying heart disease, are associated with an increased risk of adverse cardiac events, particularly sustained ventricular dysrhythmias and sudden death.

• In patients who have had a MI, the risk of malignant ventricular arrhythmias and sudden death is related to the complexity and frequency of the PVCs. Patients with PVCs in Lown classes 3-5 are at greatest risk (see Lown grading criteria below).

Race: African American race is associated with an increased frequency of PVCs on routine monitoring. In a large population-based study of PVC prevalence, African American race alone increased the risk of PVCs by 30% compared with the risk in white individuals.

Sex: Ventricular ectopy is more prevalent in men than in women of the same age. Male sex alone increases the risk of identifying PVCs on routine screening, with an odds ratio for male sex of 1.39 compared with women.

Age: PVC frequency increases with age, reflecting the increased prevalence of hypertension and cardiac disease in aging populations.

CLINICAL

Section 3 of 12

History: The important elements in obtaining a history from patients with ventricular ectopy are a history of cardiac disease or structural heart disease. Current medications that may be proarrhythmic or that may increase the risk of abnormal potassium or magnesium levels and use of drugs or medications that are sympathomimetic (eg, ephedrine-containing products, cocaine), may also provide important clues to the source of the PVCs.

Symptoms pertinent to the management of the PVC's are those that suggest underlying ischemic cardiac disease, such as chest pain or its anginal equivalent, or those suggesting hemodynamic compromise, such as lightheadedness or syncope.

• Patients are usually asymptomatic.

• Cannon A waves or the increased force of contraction due to postextrasystolic potentiation of contractility can cause palpitations and neck and/or chest discomfort.

• The patient may report feeling that his or her heart "stops" after a PVC.

• Patients with frequent PVCs or bigeminy may report syncope. This symptom is due to either inadequate stroke volume or decreased cardiac output caused by the condition effectively halving the heart rate.

• Long runs of PVCs can result in hypotension.

• Exercise can increase or decrease the PVC rate.

Physical: Important findings on the physical examination are those that provide clues to the underlying cause of the ventricular ectopy.

• Blood pressure: Frequent PVCs may result in hemodynamic compromise. Frank hypotension is rare, but relative hypotension is not uncommon, particularly in patients with underlying cardiac disease.

• Pulse: The ectopic beat may produce a diminished or absent pulse depending on the force of the ventricular contraction.

• Pulse oximetry: Hypoxia may precipitate PVCs.

• Cardiac findings: Cannon A waves may be observed in the jugular venous pulse if the timing of the PVC causes an atrial contraction against a closed tricuspid valve.

• Cardiopulmonary findings: Findings in conjunction with longstanding hypertension (elevated BP and an S4) or CHF (S3 and rales) are important clues to the cause and clinical significance of PVCs.

• Neurologic findings: Agitation and findings of sympathetic activation (eg, dilated pupils, warm and dry skin, tremor, tachycardia, hypertension) suggest that catecholamines may be the cause of the ectopy.

Causes:

• Cardiac

• Acute MI or ischemia

• Myocarditis

• Cardiomyopathy, dilated or hypertrophic

• Myocardial contusion

• Mitral valve prolapse

• Hypoxia and/or hypercapnia

• Medications (eg, digoxin, sympathomimetics, tricyclic antidepressants, aminophylline, caffeine)

• Illicit substances (eg, cocaine, amphetamines, alcohol, tobacco)

• Hypomagnesemia, hypokalemia, hypercalcemia

DIFFERENTIALS

Section 4 of 12

Acute Coronary Syndrome
Myocardial Infarction
Myocarditis
Ventricular Fibrillation
Ventricular Tachycardia

WORKUP

Section 5 of 12

Lab Studies:

• Obtain serum electrolyte levels, in particular potassium levels. Consider checking the magnesium level, especially in patients with low potassium levels.

• In selected patients, a drug screen may be helpful.

• For patients taking medication with known proarrhythmic effects (eg, digoxin, theophylline), drug levels may be useful.

Other Tests:

• ECG allows the physician to characterize the ventricular ectopy and determine its cause. In addition to the standard 12-lead ECG, a 2-minute rhythm strip may help in determining frequency of the ectopy and capture infrequent PVCs. Findings may include the following:

• Left ventricular hypertrophy

• Active cardiac ischemia (ST-segment depression or elevation and or T-wave inversion)

• In patients with previous MI - Q waves or loss of R waves, bundle branch block

• Electrolyte abnormalities (hyperacute T waves, QT prolongation)

• Drug effects (QRS widening, QT prolongation)

• On ECG, PVCs may be premature in relation to the next expected beat of the basic rhythm. The pause after the premature beat is usually a fully compensatory pause. The R-R interval surrounding the premature beat is equal to double the basic R-R interval, showing that the ectopic beat did not reset the sinus node.

• PVCs may appear in a pattern of bigeminy, trigeminy, or quadrigeminy, which describe a pattern of PVCs occurring every other, every third, or every fourth beat, respectively.

• PVCs with identical morphologies on a tracing are called monomorphic or unifocal. If the PVCs demonstrate 2 or more different morphologies, they are referred to as multiform, pleomorphic, or polymorphic.

• PVCs usually are described in terms of the Lown grading system for premature beats. The higher the grade, the more serious the ectopy.
  • Grade 0 = No premature beats

  • Grade 1 = Occasional ( <30/h)

  • Grade 2 = Frequent (>30/h)

  • Grade 3 = Multiform

  • Grade 4 = Repetitive (A = Couplets, B = Salvos of = or > 3)

  • Grade 5 = R-on-T pattern

• Holter 24-hour monitors are useful in quantifying and characterizing ventricular ectopy.

• Holters also have been used to determine treatment efficacy in patents with frequent or complex PVCs.

• Suppression of ectopy on Holter monitoring is not always predictive of survival.

• The most important role for Holter monitoring is risk stratification of patients with a recent MI or known left ventricular dysfunction.

• More than 60% of healthy, middle-aged men have ventricular ectopy on Holter monitoring.

• Signal-averaged ECG

• Signal-averaged ECGs (SAECGs) may have a future role in identifying patients at risk for complex ventricular ectopy and nonsustained ventricular tachycardia (NSVT).

• SAECGs may have a role in identifying patients with complex ectopy who may benefit from electrophysiologic studies (EPS).

• Echocardiography is useful not only in evaluating the ejection fraction, which is important in determining the prognosis and also in identifying valvular disease or ventricular hypertrophy.

Procedures:

• Exercise stress testing (EST) is best used complementary to Holter monitoring. In patients with complex ectopy, EST can unmask NSVT triggered by increased catecholamines or myocardial ischemia.

• The role of EPS in complex ventricular ectopy is an area of both intense research and debate. A joint American Heart Association (AHA)/American College of Cardiology (ACC) statement suggested the following:

• Routine EPS are not indicated in low-risk patients after MI. Low risk refers to simple ectopy, good left ventricular function, and low congestive heart failure (CHF) class.

• EPS are indicated in high-risk patients with complex ectopy.

• EPS are though to be beneficial in patients with sustained ventricular tachycardia more than 24 hours after MI.

TREATMENT

Section 6 of 12

Prehospital Care:

• Perform telemetry.

• Secure intravenous (IV) access.

• Administer oxygen.

• Complex ectopy in the setting of myocardial ischemia or causing hemodynamic instability should be suppressed. Use lidocaine for patients with myocardial ischemia.

Emergency Department Care:

• The decision to treat PVCs in the emergency or outpatient settings depends on the clinical scenario. In the absence of cardiac disease, isolated, asymptomatic ventricular ectopy, regardless of configuration or frequency, requires no treatment. With cardiac disease, certain toxic effects, and electrolyte imbalances, treatment may be required. Establish telemetry and IV access, initiate oxygen, and obtain a 12-lead ECG.

• Hypoxia: Treat the underlying cause; secure the ABCs and provide oxygen.

• Drug toxicity: Specific therapy is indicated for certain toxic effects. Examples include digoxin (Fab antibodies), tricyclics (bicarbonate), and aminophylline (GI decontamination and possibly hemodialysis).

• Correct electrolyte imbalances, particularly those of magnesium, calcium, and potassium.

• Acute ischemia and/or infarction

• Early diagnosis and treatment of acute infarction/ischemia are the cornerstones of therapy.

• The routine use of lidocaine and other type I antiarrhythmic agents in the setting of acute MI is no longer recommended because of their toxic effects.

• Acute ischemia or infarction includes patients with ectopy in the period immediately after receiving thrombolytic agents, during which complex ectopy frequently is seen.

• Only in the setting of symptomatic, complex ectopy is lidocaine likely to benefit a patient having an MI.

• Beta-blockers have proven efficacy in the setting of acute MI and are safe to use.

Consultations: Involvement of a cardiologist may be indicated if the patient’s condition is refractory to standard therapy.

MEDICATION

Section 7 of 12

Therapy for complex ventricular ectopy depends on the setting and the underlying cause. In drug toxicity, specific therapies are available. With electrolyte imbalances, correction of abnormalities is therapeutic. Lidocaine is the drug of choice (DOC) in the setting of complex ectopy in the peri-MI period if the patient is symptomatic, yet no firm evidence supports this practice.

Drug Category: Antiarrhythmics -- These agents alter the electrophysiologic mechanisms responsible for PVCs.

Drug Name	Lidocaine (Dilocaine) -- Class IB agent that stabilizes cell membranes and blunts phase 0 of action potential and shortens repolarization. Net effect is to decrease firing of ectopic foci and allow normal rhythm to reassert itself.
Adult Dose	1-1.5 mg/kg IV bolus; repeat 1.5 mg/kg boluses q3-5min prn to total of 3 mg/kg; follow with 2 mg/min continuous IV infusion after return of perfusion; if continuous infusion not started, additional boluses of 0.5 mg/kg should be administered q10min to maintain effect ET dose is 2-2.5 times IV dose
Pediatric Dose	Loading dose: 1 mg/kg IV/ET/IO; repeat twice q10-15min prn Maintenance dose: 20-50 mcg/kg/min continuous IV infusion
Contraindications	Documented hypersensitivity; Adams-Stokes syndrome; Wolff-Parkinson-White syndrome; severe sinoatrial, AV, or intraventricular block, if artificial pacemaker not in place
Interactions	Cimetidine or beta-blockers increase toxicity; procainamide or tocainide may result in additive cardiodepressant action; may increase effects of succinylcholine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Use solution without preservatives; caution in CHF, hepatic disease, hypoxia, hypovolemia or shock, respiratory depression, and bradycardia; may increase risk of CNS and adverse cardiac effects in elderly; high plasma concentrations can cause seizures, heart block, and AV conduction abnormalities

Drug Name	Procainamide (Procanbid) -- Class IA agent for PVCs. Increases refractory period of atria and ventricles. Myocardial excitability reduced by increasing threshold for excitation and inhibition of ectopic pacemaker activity.
Adult Dose	30 mg/min IV infusion until arrhythmia suppressed, hypotension occurs, QRS widens 50% above baseline, or maximum dose of 17 mg/kg administered After arrhythmia suppressed, may continuously infuse at 1-4 mg/min
Pediatric Dose	Not established; following doses have been suggested: 15-50 mg/kg/d PO divided q3-6h; not to exceed 4 g/d 3-6 mg/kg/dose IV infused over 5 min 20-30 mg/kg/d IM divided q4-6h; not to exceed 4 g/d Maintenance: 20-80 mcg/kg/min continuous infusion; not to exceed 100 mg/dose or 2 g/d
Contraindications	Documented hypersensitivity; complete heart block or second- or third-degree heart block (if pacemaker not in place); torsade de pointes; systemic lupus erythematosus
Interactions	Cimetidine, ranitidine, beta-blockers, amiodarone, trimethoprim, and quinidine increase levels of procainamide metabolite NAPA; may increase effect of skeletal muscle relaxants, quinidine, lidocaine, and neuromuscular blockers; ofloxacin inhibits tubular secretion and may increase bioavailability; sparfloxacin may increase risk of cardiotoxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Monitor for hypotension; plasma concentrations of procainamide and active metabolite NAPA may increase in renal failure; high or toxic concentrations may induce AV block or abnormal automaticity; caution in complete AV block, digitalis intoxication, organic heart disease, renal disease, and hepatic insufficiency

Drug Name	Bretylium (Bretylate) -- Class III agent for treatment of PVCs. Because of catecholamine-releasing properties and adverse effects, should not be used as initial treatment. Limit use to PVCs refractory to class I antiarrhythmics. Increases fibrillation threshold and causes refractory period by decreasing potassium conductance.
Adult Dose	5.0 mg/kg (undiluted) IV over 1 min; 10 mg/kg (undiluted) over 1 min for persistent arrhythmia; repeat q15-30min prn; not to exceed 30-35 mg/kg/24h Maintenance: 1.0-2.0 mg/min
Pediatric Dose	Not established Suggested dose: 10 mg/kg over 1 min IV q15min prn; not to exceed 30 mg/kg Maintenance: 5-10 mg/kg/dose IV q6h
Contraindications	Documented hypersensitivity; systemic lupus erythematosus; digitalis-induced arrhythmias; complete heart block or second- or third-degree heart block if pacemaker not in place; torsade de pointes
Interactions	Pressor catecholamines and digitalis may increase toxicity; ofloxacin may increase risk of cardiotoxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	May cause hypotension, especially in patients with fixed cardiac output (eg, aortic stenosis); caution in renal insufficiency, severe pulmonary hypertension, and aortic stenosis; half-life increases in the elderly; with renal clearance of 10-50 mL/min, administer 25-50% of usual dose; rapid IV injections may result in transient hypertension, nausea, and vomiting; limit injection to 5 mL (undiluted) at each injection site

Drug Category: Beta-adrenergic blockers -- This category of drugs has the potential to suppress ventricular ectopy due to ischemia or excess catecholamines. In myocardial ischemia, beta-blockers have antiarrhythmic properties and reduce myocardial oxygen demand secondary to elevations in heart rate and inotropy.

Drug Name	Metoprolol (Lopressor) -- Selective beta1-adrenergic receptor blocker that decreases automaticity of contractions. During IV administration, carefully monitor BP, heart rate, and ECG.
Adult Dose	5 mg IV q2min for 3 bolus injections
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; uncompensated CHF; bradycardia; asthma; cardiogenic shock; AV conduction abnormalities
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effects; sparfloxacin, phenothiazines, astemizole (withdrawn from US market), calcium channel blockers, quinidine, flecainide, and contraceptives may increase toxicity; may increase toxicity of digoxin, flecainide, clonidine, epinephrine, nifedipine, prazosin, verapamil, and lidocaine
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Beta-adrenergic blockade may reduce signs and symptoms of acute hypoglycemia and may decrease clinical signs of hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; monitor patient closely and withdraw drug slowly; during IV administration, carefully monitor BP, heart rate, and ECG

Drug Name	Esmolol (Brevibloc) -- Excellent drug for patients at risk of complications from beta-blockade, particularly those with reactive airway disease, mild-moderate left ventricular dysfunction, and/or peripheral vascular disease. Short half-life of 8 min allows for titration to desired effect and quick discontinuation if necessary.
Adult Dose	Loading dose: 500 mcg/kg/min IV infusion for 1 min Maintenance dose: 50 mcg/kg/min IV infusion for 4 min; if adequate therapeutic effect not observed within 5 min, repeat loading dose and follow with maintenance infusion of 100 mcg/kg/min IV; continue titration procedure, repeating loading infusion and increasing maintenance infusion by 50 mcg/kg/min (for 4 min); as desired heart rate or therapeutic end point (eg, lowered BP) approached, omit loading infusion and reduce incremental dose in maintenance infusion from 50 mcg/kg/min to 25 mcg/kg/min or lower; if desired, increase interval between titration steps from 5 to 10 min
Pediatric Dose	Not established Suggested dose: 100-500 mcg/kg IV; administered over 1 min
Contraindications	Documented hypersensitivity; cardiogenic shock; CHF; bradycardia; AV conduction abnormalities
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease bioavailability and plasma levels, possibly resulting in decreased pharmacologic effect; sparfloxacin, astemizole (withdrawn from US market), calcium channel blockers, quinidine, flecainide, and contraceptives may increase cardiotoxicity; digoxin, flecainide, acetaminophen, clonidine, epinephrine, nifedipine, prazosin, haloperidol, phenothiazines, and catecholamine-depleting agents increase toxicity
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockers may mask signs and symptoms of acute hypoglycemia and clinical signs of hyperthyroidism; symptoms of hyperthyroidism, including thyroid storm, may worsen when medication abruptly withdrawn; withdraw drug slowly and monitor patient closely

Drug Name	Propranolol (Inderal) -- Class II antiarrhythmic, nonselective beta-adrenergic receptor blocker with membrane-stabilizing activity that decreases automaticity of contractions.
Adult Dose	1-3 mg (with careful monitoring) IV; not to exceed 1 mg/min to avoid lowering BP and causing cardiac standstill Allow time for drug to reach site of action (particularly if slow circulation); administer second dose after 2 min prn; thereafter, do not give additional drug in <4 h Do not continue doses after desired alteration in rate or rhythm achieved; switch to PO ASAP; 10-30 mg tid/qid PO usual dose
Pediatric Dose	2-4 mg/kg/d PO divided bid (ie, 1-2 mg/kg bid) IV use not recommended; however, for arrhythmias, dose of 0.01-0.1 mg/kg IV has been recommended; not to exceed 1 mg/dose by slow push; change to PO ASAP
Contraindications	Documented hypersensitivity; uncompensated CHF; cardiogenic shock; bradycardia; AV conduction abnormalities
Interactions	Aluminum salts, barbiturates, NSAIDs, penicillins, calcium salts, cholestyramine, and rifampin may decrease effects; calcium channel blockers, cimetidine, loop diuretics, and MAOIs may increase toxicity; may increase toxicity of hydralazine, haloperidol, benzodiazepines, and phenothiazines
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Beta-adrenergic blockade may decrease signs of acute hypoglycemia and hyperthyroidism; abrupt withdrawal may exacerbate symptoms of hyperthyroidism, including thyroid storm; withdraw drug slowly and monitor closely

Drug Name	Amiodarone (Cordarone) -- Class III antiarrhythmic. Has antiarrhythmic effects that overlap all 4 Vaughn-Williams antiarrhythmic classes. May inhibit AV conduction and sinus node function. Prolongs action potential and refractory period in myocardium and inhibits adrenergic stimulation. Only agent proven to reduce incidence and risk of cardiac sudden death, with or without obstruction to LV outflow. Effective in converting atrial fibrillation and flutter to sinus rhythm and in suppressing recurrence; low risk of proarrhythmia effects, and any proarrhythmic reactions generally are delayed. Used in patients with structural heart disease. Most clinicians comfortable with inpatient or outpatient loading with 400 mg PO tid for 1 wk because of low proarrhythmic effect, followed by weekly reductions with goal of lowest dose with desired therapeutic benefit (usual maintenance dose 200 mg/d). During loading, patients must be monitored for bradyarrhythmias. Before administration, control the ventricular rate and CHF (if present) with digoxin or calcium channel blockers. Oral efficacy may take weeks. With exception of disorders of prolonged repolarization (eg, LQTS), may be DOC for life-threatening ventricular arrhythmias refractory to beta-blockade and initial therapy with other agents.
Adult Dose	150 mg IV over 10 min, then 1 mg/min continuous infusion for 6 h, then maintenance infusion at 0.5 mg/min IV Oral dosing generally 400 mg/d after load
Pediatric Dose	Not established; weight-based dosing suggested; consider for refractory ventricular arrhythmias in children
Contraindications	Documented hypersensitivity; complete AV block and intraventricular conduction defects; patients taking ritonavir or sparfloxacin
Interactions	Increases effect and blood levels of theophylline, quinidine, procainamide, phenytoin, methotrexate, flecainide, digoxin, cyclosporine, beta-blockers, and anticoagulants; cardiotoxicity of amiodarone is increased by ritonavir, sparfloxacin, and disopyramide; coadministration with calcium channel blockers, may cause an additive effect and decrease myocardial contractility further; cimetidine may increase amiodarone levels; protease inhibitors (eg, indinavir, ritonavir, amprenavir, nelfinavir) inhibit amiodarone metabolism resulting in increased serum levels and may prolong QT interval; coadministration may increase myopathy/rhabdomyolysis risk associated with HMG-CoA reductase inhibitors (eg, simvastatin); other drugs that prolong the QT interval (eg, fluoroquinolones, erythromycin, dofetilide, tricyclic antidepressants, thioridazine) may increase life-threatening arrhythmia risk
Pregnancy	D - Unsafe in pregnancy
Precautions	Known to cause serious (possibly fatal) toxicities, including pulmonary and liver toxicities; may cause prolonged proarrhythmic effects; may cause optic neuritis/neuropathy or hypothyroidism or hyperthyroidism; CNS and GI toxicity may occur and typically dissipates with dose reduction

Drug Category: Electrolytes -- These agents are considered to be therapeutic alternatives for refractory PVCs. Patients with persistent or recurrent PVCs following antiarrhythmic administration should be assessed for underlying electrolyte abnormalities as a cause for their refractory dysrhythmias. Hypomagnesemia is associated with the onset of PVCs.

Drug Name	Magnesium sulfate -- Acts as antiarrhythmic agent; diminishes frequency of PVCs, particularly those due to acute ischemia.
Adult Dose	1-2 g diluted in 100 mL of D5W over 1-2 min for refractory ventricular fibrillation and known or suspected hypomagnesemia (magnesium <1.4 mEq/L); not to exceed 30-40 g/d, or maintenance infusion of 1-2 g/h
Pediatric Dose	Not established Suggested dose for hypomagnesemia: 25-50 mg/kg/dose q4-6h for 3-4 doses; maximum single dose of 2 g may also be administered and repeated if hypomagnesemia persists
Contraindications	Documented hypersensitivity; heart block; Addison disease; myocardial damage; severe hepatitis
Interactions	Nifedipine may cause hypotension and neuromuscular blockade; may increase neuromuscular blockade seen with aminoglycosides and potentiate neuromuscular blockade produced by tubocurarine, vecuronium, and succinylcholine; may increase CNS effects and toxicity of CNS depressants and betamethasone; may increase cardiotoxicity of ritodrine
Pregnancy	A - Safe in pregnancy
Precautions	May alter cardiac conduction, leading to heart block in patients receiving digitalis; respiratory rate, deep tendon reflex, and renal function should be monitored when electrolyte administered parenterally; caution when administering dose, as may produce significant hypertension or asystole; in overdose, may give calcium gluconate 10% solution as antidote for clinically significant hypermagnesemia

Drug Category: Calcium channel blockers -- Calcium is involved in the generation of action potentials in specialized automatic and conducting cells in the heart. The calcium channel blockers share the ability to inhibit movement of calcium ions across the cell membrane. This effect can depress both impulse formation (automaticity) and conduction velocity.

Drug Name	Verapamil (Calan, Covera, Verelan) -- Can diminish PVCs associated with perfusion therapy and decrease risk of ventricular fibrillation and ventricular tachycardia. By interrupting reentry at AVN, can restore normal sinus rhythm in paroxysmal supraventricular tachycardia.
Adult Dose	80-160 mg PO tid
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity; severe CHF; sick sinus syndrome; second- or third-degree AV block; hypotension (<90 mm Hg systolic)
Interactions	May increase levels of carbamazepine, digoxin, and cyclosporine; amiodarone can cause bradycardia and decrease in cardiac output; beta-blockers may increase cardiac depression; cimetidine may increase levels; may increase theophylline levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Hepatocellular injury may occur; transient elevations of transaminases with or without elevations in alkaline phosphatase and bilirubin have occurred (elevations transient and may disappear with continued treatment); monitor liver function periodically

FOLLOW-UP

Section 8 of 12

Prognosis:

• In asymptomatic patients without underlying heart disease, the long-term prognosis is similar to that of the general population. Asymptomatic patients with ejection fractions greater than 40% have a 3.5% incidence of sustained ventricular tachycardia or cardiac arrest. Therefore, in patients with absence of heart disease on noninvasive workup, reassurance is appropriate.

• In the setting of acute coronary ischemia/infarction, patients with simple PVCs rarely progress to malignant arrhythmias. However, persistent complex ectopy after MI is associated with increased risk of sudden death and may be an indication for EPS.

• Patients with underlying chronic structural heart disease (eg, cardiomyopathy, infarction, valvular disease) and complex ectopy (eg, >10 PVCs/h) have a significantly increased rate of mortality.

• Understanding of the role of antiarrhythmic therapy in the months after MI is poor. The Cardiac Arrhythmia Suppression Trial (CAST) studied patients with ventricular ectopy after MI to see if antiarrhythmic therapy improved survival rates. Despite suppression of ectopy on Holter monitoring, patients treated with encainide, flecainide, or moricizine had increased rates of sudden death and death from all causes. Findings have suggested a role for amiodarone in this patient population and have had significant reductions in rates of post-MI ventricular arrhythmias and death.

• Left ventricular dysfunction has a stronger association with increased mortality rate than do PVCs. Many now believe that PVCs reflect the severity of heart disease rather than contribute to arrhythmogenesis.

• EPS has a primary role in risk stratification of patients with frequent or complex PVCs. Patients with PVCs that are noninducible (ie, unable to trigger ventricular tachycardia during stimulation) have a low risk of sudden death.

MISCELLANEOUS

Section 9 of 12

Special Concerns:

• Children

• PVCs are less common in children than in adults, but PVCs do occur in healthy children.

• About 20% of healthy boys aged 10-13 years have PVCs on routine Holter monitoring.

• PVCs in healthy newborns generally resolve by the 12th week and usually require no treatment once the presence of a healthy heart is confirmed. This finding probably is related to developmental factors associated with the autonomic nervous system.

• In older children, PVCs often are related to transient or exogenous factors, including mild viral myocarditis, excessive caffeine, or sympathomimetic drugs (cold or asthma medications). They usually resolve without treatment.

• When complex ectopy is seen in pregnancy, or immediately after, obtain an ECG for possible peripartum cardiomyopathy.

• Closely monitor and admit to an appropriate monitored setting patients with presentations that indicate an ischemic basis for their PVCs (eg, chest pain, dyspnea, syncope) or who are hemodynamically unstable while in the ED.

TEST QUESTIONS

Section 10 of 12

CME Question 1: Which of the following is not considered complex ventricular ectopy?

A: Couplets
B: Nonsustained ventricular tachycardia
C: Premature ventricular contraction (PVC) occurring on the middle of the T wave
D: Unifocal PVCs
E: None of the above

The correct answer is D: Unifocal or monomorphic PVCs are not considered complex unless 3 or more occur in a row, in which case they are called nonsustained ventricular tachycardia.

CME Question 2: Which of the following statements about premature ventricular contraction (PVC) is inaccurate?

A: Lidocaine is not indicated prophylactically in patients presenting with chest pain.
B: Lidocaine is indicated for simple premature ventricular contractions (PVCs) in the setting of acute myocardial infarction.
C: Asymptomatic patients with no evidence of cardiac disease but with frequent ectopy do not have a significantly increased rate of mortality when compared to the general population.
D: A PVC is not always followed by a fully compensatory pause.
E: None of the above

The correct answer is B: Patients with simple PVCs in the setting of acute myocardial infarction should not be treated routinely with lidocaine because of its significant toxicity. Lidocaine is the drug of choice in the setting of complex ectopy in the peri-MI period if the patient is symptomatic, yet no firm evidence supports this practice.

Pearl Question 1 (T/F): Less than 50% of healthy, middle-aged men have ventricular ectopy on Holter monitoring.

The correct answer is False: More than 60% of healthy, middle-aged men have ventricular ectopy on Holter monitoring. About 20% of healthy boys aged 10-13 years have PVCs on routine Holter monitoring.

Pearl Question 2 (T/F): Complex ectopy is a better prognosticator of sudden cardiac death than ejection fraction.

The correct answer is False: A patient’s ejection fraction and congestive heart failure (CHF) class are far better prognosticators of sudden cardiac death than the presence of complex ventricular ectopy.

Pearl Question 3 (T/F): Cocaine, amphetamines, and ethanol are some common exogenous causes of ventricular ectopy in young, healthy persons.

The correct answer is True: In young, healthy persons, always consider exogenous etiologies (eg, cocaine, amphetamines, ethanol, digoxin, sympathomimetics, tricyclic antidepressants, caffeine).

Pearl Question 4 (T/F): In patients with chronic left ventricular dysfunction and complex ectopy, suppression of ectopy improves mortality rate.

The correct answer is False: The Cardiac Arrhythmia Suppression Trial (CAST) demonstrated that suppression of ectopy does not always lead to improvement in mortality rate. This is partially due to the proarrhythmic effects of some of the antiarrhythmic agents and partially to the profound toxic effects of many of the agents.

PICTURES

Section 11 of 12

Caption: Picture 1. ECG shows frequent, unifocal PVCs with a fixed coupling interval between the ectopic beat and the previous beat. These PVCs result in a fully compensatory pause; the interval between the 2 sinus beats surrounding the PVC are exactly twice the normal R-R interval. This finding indicates that the sinus node continues to pace at its normal rhythm despite the PVC, which fails to reset the sinus node.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: ECG
Caption: Picture 2. On this ECG, the PVCs occur near the peak of the T wave of the preceding beat. These beats predispose the patient to ventricular tachycardia or fibrillation. This R-on-T pattern is often seen in patients with acute myocardial infarction or long Q-T intervals. In the latter case, the triggered arrhythmia would be torsade.
	View Full Size Image
	eMedicine Zoom View (Interactive!)
Picture Type: ECG

BIBLIOGRAPHY

Section 12 of 12

• Burkart F, Pfisterer M, Kiowski W, et al: Effect of antiarrhythmic therapy on mortality in survivors of myocardial infarction with asymptomatic complex ventricular arrhythmias: Basel Antiarrhythmic Study of Infarct Survival (BASIS). J Am Coll Cardiol 1990 Dec; 16(7): 1711-8[Medline].
• Cairns JA, Connolly SJ, Roberts R, Gent M: Randomised trial of outcome after myocardial infarction in patients with frequent or repetitive ventricular premature depolarisations: CAMIAT. Canadian Amiodarone Myocardial Infarction Arrhythmia Trial Investigators. Lancet 1997 Mar 8; 349(9053): 675-82[Medline].
• Califf RM, McKinnis RA, Burks J, et al: Prognostic implications of ventricular arrhythmias during 24 hour ambulatory monitoring in patients undergoing cardiac catheterization for coronary artery disease. Am J Cardiol 1982; 50: 23-31[Medline].
• CAST Investigators: Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. N Engl J Med 1989 Aug 10; 321(6): 406-12[Medline].
• Hallstrom AP, Bigger JT Jr, Roden D, et al: Prognostic significance of ventricular premature depolarizations measured 1 year after myocardial infarction in patients with early postinfarction asymptomatic ventricular arrhythmia. J Am Coll Cardiol 1992 Aug; 20(2): 259-64[Medline].
• Hammill SC, Trusty JM, Wood DL, et al: Influence of ventricular function and presence or absence of coronary artery disease on results of electrophysiologic testing for asymptomatic nonsustained ventricular tachycardia. Am J Cardiol 1990 Mar 15; 65(11): 722-8[Medline].
• Hargarten K, Chapman PD, Stueven HA, et al: Prehospital prophylactic lidocaine does not favorably affect outcome in patients with chest pain. Ann Emerg Med 1990 Nov; 19(11): 1274-9[Medline].
• Jouven X, Zureik M, Desnos M, et al: Long-term outcome in asymptomatic men with exercise-induced premature ventricular depolarizations. N Engl J Med 2000 Sep 21; 343(12): 826-33[Medline].
• Kennedy HL, Whitlock JA, Sprague MK, et al: Long-term follow-up of asymptomatic healthy subjects with frequent and complex ventricular ectopy. N Engl J Med 1985 Jan 24; 312(4): 193-7[Medline].
• Lown B, Wolf M: Approaches to sudden death from coronary heart disease. Circulation 1971 Jul; 44(1): 130-42[Medline].
• Maggioni AP, Zuanetti G, Franzosi MG, et al: Prevalence and prognostic significance of ventricular arrhythmias after acute myocardial infarction in the fibrinolytic era. GISSI-2 results. Circulation 1993 Feb; 87(2): 312-22[Medline].
• Rehnqvist N, Olsson G, Erhardt L, Ekman AM: Metoprolol in acute myocardial infarction reduces ventricular arrhythmias both in the early stage and after the acute event. Int J Cardiol 1987 Jun; 15(3): 301-8[Medline].
• Simpson RJ, Cascio WE, Schreiner PJ, et al: Prevalence of premature ventricular contractions in a population of African American and white men and women: the Atherosclerosis Risk in Communities (ARIC) study. Am Heart J 2002 Mar; 143(3): 535-40[Medline].
• Teo KK, Yusuf S, Furberg CD: Effects of prophylactic antiarrhythmic drug therapy in acute myocardial infarction. An overview of results from randomized controlled trials. JAMA 1993 Oct 6; 270(13): 1589-95[Medline].

eMedicine Journals > Emergency Medicine > Cardiovascular > Premature Ventricular Contraction

Please email us with any comments you have on our new chapter format.

Author Information | Introduction | Clinical | Differentials | Workup | Treatment | Medication | Follow-up | Miscellaneous | Test Questions | Pictures | Bibliography