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The diagnosis and management of ventricular arrhythmias

Kurt C. Roberts-Thomson, Dennis H. Lau and Prashanthan Sanders
Abstract | The term ventricular arrhythmias incorporates a wide spectrum of abnormal cardiac rhythms, from single premature ventricular complexes to sustained monomorphic ventricular tachycardia (VT), polymorphic VT, and ventricular fibrillation. Sustained ventricular arrhythmias are the most common cause of sudden cardiac death. These arrhythmias occur predominantly in patients with structural heart disease, but are also seen in patients with no demonstrable cardiac disease. The diagnosis of VT can be made reliably using electrocardiographic criteria, and a number of algorithms have been proposed. Among patients with VT and a structurally normal heart, the prognosis is usually benign and treatment is predominantly focused on the elimination of symptoms. Patients who have VT in the presence of structural heart disease are often managed with implantable cardioverter-defibrillators. These devices are effective for both primary and secondary prevention of VT and sudden cardiac death. Pharmacological therapy for VT has limited efficacy and is associated with a high incidence of adverse effects. Radiofrequency catheter ablation is useful for controlling recurrent episodes of monomorphic VT; however, research is needed to define the role of catheter ablation in the treatment of other ventricular arrhythmias.
Roberts-Thomson, K. C. et al. Nat. Rev. Cardiol. advance online publication 22 February 2011; doi:10.1038/nrcardio.2011.15

Introduction

Sustained ventricular arrhythmias are an important cause of morbidity and the most common cause of sudden cardiac death, accounting for 7580% of cases.13 The term ventricular arrhythmias incorporates a wide spectrum of abnormal cardiac rhythms, from single premature ventricular complexes (PVCs) to sustained monomorphic ventricular tachycardia (VT), polymorphic VT, and ventricular fibrillation. These arrhythmias predominantly occur in patients with structural heart diseases, such as ischemic and dilated cardiomyopathies. However, benign forms of VT can also occur among individuals without evidence of cardiac disease. Evaluation of the underlying disease substrate is important, as the etiology not only provides clues to the mechanism of the arrhythmia, but also determines the patients prognosis and the appropriate therapy, which differ between the various forms of ventricular arrhythmia. Patients with VT most commonly present with a wide QRS complex during tachycardia. The electrocardiographic characteristics of the arrhythmia can indicate potential mechanisms and the nature of the underlying etiology. Sustained monomorphic VT has a repetitive sequence of ventricular activation and, therefore, a QRS
Competing interests K. C. Roberts-Thomson declares an association with the following company: St Jude Medical. P. Sanders declares associations with the following companies: Bard Electrophysiology, Biosense-Webster, Medtronic, Merck Sharp & Dohme, Sanofi-Aventis and St Jude Medical. See the article online for full details of the relationships. D. H. Lau declares no competing interests.

morphology that does not change from beat to beat. This pattern can indicate a single focus that initiates ventricular activation, or a stable substrate capable of supporting a reentrant circuit. Both mechanisms can occur in patients with or without structural heart disease. By contrast, polymorphic VT has continuously changing QRS morphology representing beat-to-beat alterations in ventricular activation. This pattern can be seen in patients without structural heart disease who have genetically based ion channel disorders, such as long QT syndromes, Brugada syndrome, catecholaminergic polymorphic VT syndrome, or idiopathic ventricular fibrillation. However, myocardial ischemia is the most common underlying etiology of polymorphic VT. In this Review, we discuss the mechanisms and diagnosis of ventricular arrhythmias and the management of these patients, focusing on monomorphic VTs.

Diagnosis of VT
Medical history and clinical examination The presentation of a patient with a wide-complex tachycardia (QRS >120 ms) is a common diagnostic dilemma in clinical practice. Several arrhythmias can present as wide-complex tachycardia, including VT, supraventricular tachycardia (SVT) with aberrancy or bundle branch block (BBB), and SVT with antegrade conduction over an accessory pathway (pre-excited tachycardia). In addition, QRS widening can be seen with other conditions, such as repaired congenital heart disease, drug toxicities, and electrolyte imbalances. However, pre-excited tachycardias, and drug-induced and electrolyte-induced
Cardiovascular Research Center, Department of Cardiology, Royal Adelaide Hospital, North Terrace, Adelaide, SA 5000, Australia (K. C. Roberts-Thomson, D. H. Lau, P. Sanders). Correspondence to: P. Sanders prash.sanders@ adelaide.edu.au

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Key points
The diagnosis of ventricular arrhythmias can be accurately made using electrocardiographic algorithms The underlying heart disease determines the prognosis of patients with ventricular arrhythmias In patients without structural heart disease, the treatment of ventricular arrhythmias is focused on the elimination of symptoms In patients with structural heart disease, implantable cardioverter-defibrillators can prevent sudden death Antiarrhythmic therapy has limited efficacy in patients with ventricular arrhythmias and can have substantial adverse effects Catheter ablation is useful to prevent recurrences of ventricular arrhythmia

such as the Valsalva maneuver or carotid sinus massage, that result in termination of tachycardia indicate the presence of SVT, but some VTs can also terminate with these maneuvers, which are, therefore, not reliable diagnostic tests.

Box 1 | Electrocardiographic findings that suggest VT

Atrioventricular dissociation Fusion or capture beats QRS width (LBBB >160 ms, RBBB >140 ms) Northwest axis Concordance LBBB morphology with right axis deviation Absence of RS complexes in precordial leads
Abbreviations: LBBB, left bundle branch block; RBBB, right bundle branch block; VT, ventricular tachycardia.

tachycardias account for only a small minority (15%) of wide-complex tachyarrhythmias and, therefore, the clinically relevant differential diagnosis is between VT and SVT with aberrancy.4 In the assessment of a patient with wide-complex tachycardia, medical history and physical examination can aid in the diagnosis. A history of angina, myocardial infarction, or congestive cardiac failure all carry a positive predictive value (PPV) for VT of >95%, but have a poorer sensitivity.5 Young patients (aged <35 years) are less likely than older patients to have VT. Age above this threshold carries a PPV of 85% and a sensitivity of 92% for VT diagnosis,5 which is to be expected given that a ventricular scar is the basis of the arrhythmia in the majority of patients with VT. Many physicians use the clinical status of the patient to help in the diagnosis of a wide-complex tachycardia; however, hemodynamic tolerance for the arrhythmia is a poor guide to diagnosis. Although VT is more likely than SVT to cause hypotension and hemodynamic collapse, these signs are not useful in differentiating between VT and SVT, and many patients with VT present with palpitations alone. Clinical examination of the patient can provide information complementary to the electrocardiogram (ECG). The clinical features of atrioventricular (AV) dissociationthe independent activation of the atria and ventriclesalmost always indicate the presence of VT. Clinical signs of AV dissociation include cannon A waves in the jugular venous pulse, variability in the intensity of the first heart sound, and variability in arterial blood pressure. These signs have reasonably good sensitivity (6196%) and specificity (71100%) for the identification of AV dissociation.6 Vagal maneuvers,
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ECG criteria The 12-lead ECG is the most reliable means of differentiating VT from SVT. As mentioned above, patients with VT usually present with a wide QRS complex during tachycardia. However, a wide-complex tachycardia with a QRS morphology consistent with either BBB or fascicular block is indicative of SVT with aberrancy, because this arrhythmia conducts through part of the HisPurkinje system. Aberrations associated with sustained tachycardias are just as likely to have a right BBB (RBBB) pattern as a left BBB (LBBB) pattern. VT is likely to be present if the QRS morphology is incompatible with these patterns.7 Therefore, the physician needs to be familiar with these QRS morphologies.8 In a few of the ECG leads, VT can seem to have a fairly narrow QRS complex and the appearance of such a narrow-complex tachycardia on a single lead does not exclude the possibility of VT. Thus, obtaining a full 12-lead ECG in patients with tachycardia is essential. A number of ECG criteria have been used to differentiate VT from SVT with aberrancy (Box 1). Heart rate is not usually a useful criterion, as both VT and SVT can occur over a wide range of heart rates. VT and SVT usually have a regular rate; a wide-complex tachycardia that is irregular is most likely to represent atrial fibrillation with BBB or antegrade conduction over an accessory pathway (Figure 1). However, irregularity of heart rate does not exclude VT. In particular, focal idiopathic VT can manifest with periods of acceleration and deceleration, and so can be irregular (Figure 2). The most useful ECG feature that differentiates VT from SVT is the presence of AV dissociation. Complete AV dissociation is present in 1050% of VTs and only in exceedingly rare cases of SVT (Figure 3). 4,911 In addition, variable retrograde conduction, in a 2:1 or Wenckebach pattern, can be seen in patients with VT. Wenckebach retrograde conduction is characterized by prolonged ventricularatrial intervals followed by a beat with AV block. The presence of AV dissociation is dependent upon the rate of the VT, and detection of this sign is dependent upon the experience of the clinician in interpreting the ECG. Fusion and capture beats during a wide-complex tachycardia imply the presence of AV dissociation (Figure 4). A fusion beat is a QRS complex arising from two different sources within the ventricle, one usually from a sinus beat propagating down the normal conduction system and one beat from the VT. A capture beat is a sinus beat that conducts down the His Purkinje system producing a narrow QRS complex during tachycardia. Both beats usually require the presence of a slow VT to affect ventricular activation. The width of the QRS complex has also been shown to be useful in diagnosing VT. In 1978, Wellens et al. observed that almost 70% of VTs had a QRS >140 ms,
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whereas all SVTs had QRS duration of <140 ms, although no patients in this study had pre-existing BBB.11 In the late 1980s, Akhtar and colleagues demonstrated that, because the QRS duration is slightly longer with LBBB, the diagnostic accuracy of using a QRS >140 ms with RBBB morphology and a QRS >160 ms with LBBB morphology is excellent, with PPVs of 100% and 96%, respectively.10 However, a relatively narrow QRS (<120 ms) does not absolutely exclude the diagnosis of VT, as can be seen when the tachycardia involves the Purkinje system. The QRS axis alone is fairly poor at differentiating VT from SVT, because block in the anterior and posterior fascicles can produce vectors between -90o and +150o, which are also commonly seen during VT. The one exception is the combination of LBBB morphology and right-axis deviation, which is almost always the result of VT.10 A right superior (Northwest) axis, which is a clear sign of VT, is present in approximately one quarter of patients.10 Single criteria are not particularly useful for differentiating between VT and SVT; therefore, a number of algorithms have been proposed for diagnostic purposes.4,9,12 The most widely used and cited is the algorithm proposed by Brugada and collegues.12 This algorithm comprises four steps, with the first two steps involving the assessment of an RS complex in the precordial leads (Figure 5a). The investigators reported that this sign had a sensitivity and specificity for the diagnosis of VT of 99% and 97%, respectively.12 Other researchers4,9 have found this algorithm to be useful, but to be less accurate than originally reported by Brugada and co-workers. In 2008, Vereckei et al. provided a simpler algorithm for the identification of VT (Figure 5b), which involves the assessment of lead aVR only.9 In a blinded comparison, this new model was found to have greater sensitivity and specificity (97% and 75%, respectively) than the widely quoted Brugada algorithm.6 Although ECG criteria are predominantly used for diagnosing VT, for cases in which doubt exists about the type of arrhythmia, an electrophysiological study can provide the diagnosis. In patients with coronary artery disease and VT, a high likelihood exists of inducing the clinical arrhythmia with reasonable reproducibility. 13 In other disease states, however, this likelihood is much lower. Isoproterenol is useful in provoking idiopathic PVCs and VT.14

Figure 1 | 12-lead electrocardiogram of atrial fibrillation with ventricular preexcitation over a left-sided accessory pathway. The morphology is right bundle branch block and Northwest axis, suggestive of ventricular tachycardia. However, the rhythm is irregular. The concordance suggests a basal location in the left ventricle for the origin of the arrhythmia. a
I II III aVR aVL V1 V2 V3 V4 V5 V6

aVF

VI II

V5

b
I aVR V1 V4

II

aVL

V2

V5

III

aVF

V3

V6

Diagnosis of structural heart disease

II

Once the diagnosis of VT has been confirmed, the prognosis of the patient and the treatment they should be given depends on the type of underlying heart disease. As will be discussed in the next section, patients without structural heart disease generally have a benign prognosis compared with patients who have various forms of cardiomyopathy.13 As a first-line investigation, transthoracic echocardiography should be performed to evaluate left and right ventricular structure and function, including left ventricular ejection fraction (LVEF). Regional wall motion abnormalities in a coronary artery distribution suggest coronary artery disease that, as the most common etiology
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Figure 2 | A patient with focal idiopathic ventricular tachycardia. a | On the 12-lead electrocardiogram (ECG), the morphology is right bundle branch block ventricular tachycardia with a left superior axis. Note the irregularity of the tachycardia, which is particularly seen with focal ventricular tachycardias. This ventricular tachycardia arose from the posterior papillary muscle in the left ventricle. b | The patients ECG during sinus rhythm is normal with no evidence of prior infarction.

of VT, needs to be excluded. Exercise stress testing, or more-commonly coronary angiography, is employed to evaluate the presence of coronary artery disease. Right ventricular abnormalities can indicate arrhythmogenic right ventricular cardiomyopathy (ARVC) or sarcoidosis.15
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I aVR V1 V4

VT in the normal heart

II

aVL

V2

V5

III

aVF

V3

V6

Idiopathic VT refers to any VT that is not associated with structural heart disease. This etiology accounts for up to 25% of patients undergoing catheter ablation of VT in the USA.19 Several forms of idiopathic VT exist, with various underlying mechanisms. Idiopathic VTs have been classified in a number of different ways, including location of origin, mechanisms, and response to pharmacological agents. Broadly, idiopathic VTs can be classified mechanistically into two groups: focal VTs, which are predominantly triggered or automatic arrhythmias, and fascicular VTs, which are predominantly re-entrant arrhythmias within the Purkinje system.

25 mm/s; 1 cm/mV

Figure 3 | 12-lead electrocardiogram of broad complex tachycardia. The diagnosis of ventricular tachycardia (VT) is made using the Brugada criteria12 and the aVR criteria.9 Note that no RS complexes are present in the precordial leads, suggesting VT. The lead aVR has an initial R wave, suggesting VT. Note the atrioventricular dissociation.
I aVR V1 V4

II

aVL

V2

V5

III

aVF

V3

V6

II

Figure 4 | 12-lead electrocardiogram of fascicular ventricular tachycardia. Note the atrioventricular dissociation, with the P waves shown with arrows. The star indicates a capture beat. This ventricular tachycardia has right bundle branch block morphology with left superior axis. The QRS is fairly narrow owing to the involvement of the Purkinje system in the mechanism of the tachycardia. Note the similar morphology to that of the focal ventricular tachycardia arising from the posterior papillary muscle (Figure 2).

Focal VT The most common form of idiopathic VT is focal VT arising from the right ventricular outflow tract, which accounts for approximately 6070% of idiopathic VTs.20 These focal VTs can manifest as recurrent PVCs or paroxysmal monomorphic VT, usually with LBBB morphology and marked inferior axis. Patients, who are typically aged 3050 years, often present with palpitations and, occasionally, presyncope. Focal VT is also observed on the ECGs of asymptomatic patients. Exercise testing reproduces the patients clinical VT in 2550% of cases.21,22 In some patients, VT is suppressed by exercise and appears during the recovery phase whereas, in other patients, VT initiates during exercise. Although the right ventricular outflow tract is the origin of the majority of focal VTs, many other sites (particularly the structures around the outflow tract regions) can also produce PVCs or paroxysmal VT (Box 2). In addition, the papillary muscles, particularly in the left ventricle, have been recognized as a fairly common site of focal VT.2326 The main differential diagnosis that needs to be excluded in patients with suspected focal VT is ARVC, which can also present as a VT with repetitive LBBB morphology. T-wave abnormalities in leads V1V3 on the baseline ECG, multiple VTs with LBBB morphology, a family history of ARVC, and right ventricular structural abnormalities support a diagnosis of ARVC.18,27
Mechanisms The majority of focal VTs seem to be caused by cyclic adeno sine monophosphate (AMP)-related activity, although the evidence for this mechanism, which was presented by Lerman and colleagues, 14,28,29 is limited. Catecholamine stimulation of the -adrenergic receptor results in a rise in intracellular cyclic AMP, producing an increase in the levels of intracellular calcium and release of calcium from the sarcoplasmic reticulum. This process then gives rise to delayed after-depolarizations and VT. Focal VTs can be induced with isoproterenol, atropine, aminophylline, and rapid pacing, but not usually with programmed ventricular stimulation.14 Other than the work by Lerman and his group, very little research has been carried out into the mechanisms of focal VT. Management The treatment of patients with focal VT depends on the frequency and severity of symptoms, as this condition has
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Cardiac MRI can provide detailed structural and functional information and is often useful, particularly in the diagnosis of ARVC and infiltrative cardiomyopathies. Myocardial fibrosis can be identified with delayed gadolinium enhancement, even in patients without prior myocardial infarction.16 In addition to providing diagnostic information, cardiac MRI can also provide prognostic information17 and has been shown to be beneficial in planning mapping and radiofrequency catheter ablation strategies.16 Myocardial biopsy and signal-averaged ECGs can also provide useful information in certain situations. In particular, myocardial biopsy can assist in the identification of ARVC or myocarditis when the diagnosis is unclear.18 The various mechanisms of VT, the prognoses and the appropriate treatments for this condition, determined by the presence or absence of structural heart disease, will be discussed separately in the following sections.
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a
Brugada algorithm Absence of RS complex in all precordial leads Yes VT diagnosed The longest RS interval >100 ms in any precordial lead Yes VT diagnosed AV dissociation Yes VT diagnosed Morphology criteria for VT present in leads V12 and V6 Yes VT diagnosed No SVT diagnosed Yes VT diagnosed No No No

aVR algorithm Presence of an initial R wave Yes VT Diagnosed Presence of an initial R or Q wave >40 ms Yes VT diagnosed Presence of notch on descending limb of a negative onset and predominantly negative QRS Yes VT diagnosed Vi/Vt 1 No SVT diagnosed No No No

Figure 5 | Electrocardiographic algorithms of broad complex tachycardia to differentiate between VT and SVT. a | Brugada algorithm. From Brugada, P. et al. A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. Circulation 83, 16491659 (1991) with permission from Wolters Kluwer Health. b | aVR algorithm. Reprinted from Heart Rhythm, 5, Vereckei, A. et al. New algorithm using only lead aVR for differential diagnosis of wide QRS complex tachycardia. 8998, copyright (2008), with permission from Elsevier. vi /vt measures the vertical excursion (in mV) recorded on the electrocardiogram during the initial (vi) and terminal (vt) 40 ms of the QRS complex. Abbreviations: AV, atrioventricular; SVT, supraventicular tachycardia; vi /vt, ventricular activation velocity ratio; VT, ventricular tachycardia.

a benign course in the vast majority of patients, with an extremely low incidence of sudden cardiac death.21,30,31 Patients with minimal symptoms do not necessarily need treatment. For those with severe symptoms or those who have developed a tachycardia-mediated cardiomyopathy, the options include pharmacological therapy or radiofrequency catheter ablation. Acute termination of focal VT can be achieved by vagal maneuvers, such as carotid sinus massage. Adenosine, lidocaine, and verapamil are also effective; both adenosine and verapamil terminate tachycardia in approximately 75% of cases.32 First-line antiarrhythmic therapy for symptomatic focal VT is usually a -blocker, often propranolol, which is effective in approximately 50% of patients. 33 Other options include calcium-channel blockers, such as verapamil and diltiazem, which are effective in 2550% of patients,3336 and class I antiarrhythmic agents, such as flecainide, which is slightly more efficacious.35,37 The most effective medications are the class III antiarrhythmic agents sotalol and amiodarone, both of which alone can eliminate symptoms in 7590% of patients.33,35,38 Radiofrequency catheter ablation is an alternative to antiarrhythmic medication in patients with symptomatic focal VT, given that many of these patients are fairly young and would otherwise require lifelong medical therapy. For VTs that arise from the right ventricular outflow tract, ablation is successful in >90% of patients.39 Ablation at
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other sites can be more challenging and occasionally is prevented by proximity to a coronary artery, resulting in slightly lower success rates. Ideally, activation mapping should be performed, but pace mapping can also be used. Activation mapping involves identifying the earliest region activated during a PVC or VT. Pace mapping involves pacing the ventricle from various sites, comparing the QRS morphology to that of the spontaneous PVC, and targeting the site with the best match. Pace mapping is predominantly used when PVCs are infrequent; however, pace map matches can often be seen over a large area, which sometimes necessitates more-extensive ablation. Complications of catheter ablation are infrequent, but include cardiac perforation and tamponade, as well as coronary artery occlusion.39,40 Reversal of tachycardiamediated cardiomyopathy can be seen following successful catheter ablation.41,42 Catheter ablation of focal VT is primarily used in patients without structural heart disease. However, ablation is also used in patients with structural heart disease and focal VT, in whom it can reduce frequent episodes of VT and improve quality of life.43

Fascicular VT Fascicular VT, which is less common than focal VT, arises from the left ventricle and presents with a RBBB morphology and predominantly left-axis deviation (Figure 4). Fascicular VT usually manifests in patients aged between
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Box 2 | Common locations of focal VT
Right ventricular outflow tract Left ventricular outflow tract Aortic cusps Pulmonary artery Mitral annulus Tricuspid annulus Papillary muscles Epicardium
Abbreviation: VT, ventricular tachycardia.

15 and 40 years, with most episodes occurring while at rest. As with focal VT, symptoms include palpitations and presyncope. Recurrent fascicular VT can lead to tachycardia-mediated cardiomyopathy, but sudden cardiac death is very rare.44,45
Mechanism The majority of evidence regarding fascicular VT comes from mapping studies and the response of tachycardia to pacing maneuvers, and indicates that the underlying mechanism is re-entry.46,47 During VT, the retrograde limb of the circuit is usually the posterior fascicle, with the antegrade limb comprising abnormal tissue in the left ventricular septum, which exhibits slow and decremental conduction. In rare cases, however, the anterior fascicle can be involved and produces right axis deviation.48 Management The prognosis of patients with fascicular VT is good and treatment is aimed at controlling symptoms. Verapamil is useful as acute therapy 49,50 although, as long-term maintenance therapy, this drug predominantly reduces symptoms rather than completely abolishing them. 44 Catheter ablation is appropriate when medications fail or are undesirable, such as among patients who cannot tolerate drug therapy, those who have comorbidities or are taking incompatible medications, and individuals who do not wish to receive medical therapy indefinitely. Longterm success rates for catheter ablation are >90%, with a low incidence of complications.5153 Catheter ablation is, therefore, the preferred strategy to avoid long-term medical therapy in patients with fascicular VT.

channels. These channels often have interstitial fibrosis, which can create separations between the muscle bundles and, therefore, circuitous patterns of activation through the bundles.54 In addition, cell-to-cell coupling between the myocytes is reduced.55 This combination creates slow conduction through the channels. In concert with the fixed anatomical obstacles created by dense fibrosis, the appropriate substrate for re-entry is set. Large ventricular scars seem to predispose the patient to the development of VT by supporting a greater number of channels than do smaller scars.56 Patients with structural heart disease and VT tend to have numerous channels, as evidenced by multiple inducible morphologies of scar-related VT.57,58 Bundle branch re-entry is a unique form of re-entrant monomorphic VT that occurs predominantly in patients with dilated cardiomyopathy. This condition comprises a macro re-entrant circuit that involves the Purkinje system. The most common form of bundle branch reentry features the right bundle as the antegrade limb and the left bundle as the retrograde limb, leading to an LBBB morphology during VT. Rarely, the circuit can occur in the opposite direction, giving rise to an RBBB pattern. Commonly, these patients have evidence of conductionsystem disease. Importantly, this form of VT responds poorly to pharmacological therapy, but can be eliminated by catheter ablation of the right bundle.5961
Primary prevention For the primary prevention of sudden cardiac arrest in patients with depressed left ventricular function, implantable cardioverter-defibrillators (ICDs) have been shown to reduce mortality compared with conventional and antiarrhythmic drug therapy. The MADIT II study,62 which included patients with ischemic cardiomyopathy and an LVEF 30%, found that ICD use reduced mortality compared with conventional therapy, with an absolute risk reduction of 5.6% and a relative risk reduction of 31%. The SCD-HeFT trial63 included patients with both ischemic and nonischemic cardiomyopathies, an LVEF of 35%, and NYHA class II or III heart failure. Patients were randomly assigned to receive an ICD, amiodarone, or conventional therapy. Although no difference in survival was found between the amiodarone-therapy and conventional-therapy groups, ICD use reduced mortality by 7.2% over 5 years compared with conventional therapy, which corresponds to a relative risk reduction of 23%.63 Acute management The initial management of a patient with sustained monomorphic VT caused by underlying structural heart disease is determined by the nature of the symptoms and the patients hemodynamic state. Regardless of the etiology, direct-current cardioversion is warranted for sustained VT, which produces symptomatic hypotension, pulmonary edema, or myocardial ischemia. Reversible causes of VT, such as electrolyte imbalances, acute ischemia, hypoxia, and drug toxicities should be corrected. In patients who are hemodynamically stable, pharmacological reversion of VT can be attempted. Lidocaine has often been regarded as a first-line antiarrhythmic agent,
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VT in structural heart disease

Sustained monomorphic VT The structural changes in the ventricles of patients with cardiac disease can create the substrate for ventricular arrhythmias. The most common substrate for VT is ventricular scarring related to ischemic heart disease, which is present in approximately 60% of patients.19 However, patients with dilated cardiomyopathies, ARVC, prior cardiac surgery (particularly for correction of congenital anomalies or valve surgery), sarcoidosis, or hypertrophic cardiomyopathy can also have ventricular scarring and VT. Ventricular scars consist of dense fibrosis, with surviving myocardial bundles traversing the scar and creating
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and can be useful in VT associated with ischemia or myocardial infarction.64 However, in patients with slow and stable VT, the efficacy of lidocaine is limited.6567 Intravenous procainamide is an appropriate therapy in these patients, as it rapidly slows and terminates VT.65 Although procainamide is successful for acute arrhythmia termination in around 75% of patients with sustained monomorphic VT, its use can be limited by hypotension, which occurs in approximately 20% of these individuals.68,69 Amiodarone is also useful, but its onset of action is slower than lidocaine or procainamide, and the results of acute termination studies have been variable. 67,7072 However, amiodarone is less likely to produce hypotension than procainamide.68 In some areas of the world, intravenous sotalol (Australia, Europe) and ajmaline (Europe) are available and have been shown to be effective.66,73 Transvenous catheter pace termination, by application of ventricular pacing at a faster rate than the VT, can also be performed to treat sustained VT. This approach is often effective and can be used in combination with antiarrhythmic agents.74,75
Secondary prevention Recurrence of VT is frequent, with approximately 50% of patients having subsequent episodes in the 2-year period following the initial event.7679 Patients who have been resuscitated from a cardiac arrest, or who have experienced VT that has produced hemodynamic compromise, have a death rate in the first year post-event of approximately 20%.80,81 In 1997, the AVID study 82 demonstrated that ICD use reduced this risk by 31% over 3 years compared with amiodarone. Whether ICDs should be used in patients who have sustained VT without hemodynamic compromise and LVEF >35% is controversial, and currently little data are available to answer this question. Although ICDs effectively treat ventricular arrhythmias, shocks from these devices can have substantial psychological consequences and may increase the risk of death.83,84 Medical therapy can also be beneficial in the secondary prevention of VT. Among patients with heart failure, who are at high risk of VT, both angiotensin-converting-enzyme inhibitors and -blockers have been shown to reduce mortality and the incidence of sudden death.8588 The class I antiarrhythmic drugs flecainide and propafenone actually increase mortality in patients at risk of ventricular arrhythmias.89,90 In patients with an ICD, amiodarone and sotalol can reduce the number of device therapies, but do not reduce mortality.63,91 Connolly and colleagues randomly assigned patients who had sustained ventricular arrhythmia, an LVEF of 40%, and an ICD, to receive a -blocker, sotalol, or amiodarone plus a -blocker.78 Over a 12-month follow-up period, ICD shocks occurred in 39% of patients in the -blocker group, 24% of those receiving sotalol, and 10% of those assigned to the combination of amiodarone and a -blocker. In addition, discontinuation rates were high in the sotalol and amiodarone groups.78 Mexiletine can be used as a second-line therapeutic agent for recurrent ventricular arrhythmias, particularly in combination with other antiarrhythmic medications, although adverse effects can limit its use.9294
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In patients with structural heart disease, catheter ablation can prevent or reduce recurrent episodes of VT without the adverse effects of antiarrhythmic therapy. Catheter ablation can also be life-saving in patients with incessant VT. As previously discussed, the arrhythmogenic regions of the ventricle are the slowly conducting channels within areas of ventricular scar. These channels are the targets of catheter ablation and can be identified in several ways. One approach is to use a combination of activation and entrainment mapping during VT. Entrainment mapping can be used to evaluate the response of the VT to pacing, to determine the relationship between the pacing site and the circuit.95 This information is useful for locating the critical portions of the circuit implicated in the arrhythmia. However, in many patients, VT is poorly tolerated or unstable and for these individuals other mapping techniques should be used during sinus rhythm. Ventricular scars can be identified by low-amplitude electrograms. This technique is used to create 3-dimensional voltage maps during sinus rhythm, which reconstruct the anatomy of the ventricle and the region of scar. Thus, abnormal electrograms within the scar, such as fractionated and late potentials representing regions of slow conduction, can be targeted during sinus rhythm allowing ablation of VTs in hemodynamically unstable patients. The majority of evidence supporting the use of catheter ablation comes from patients with ischemic cardiomyopathies and VT. In this group, success rates range from 50% to 80%, with the incidence of major complications being up to 10%.57,58 Procedure-related mortality is low, and most deaths result from failure of the procedure to control life-threatening arrhythmias.58 Catheter ablation is also beneficial in controlling recurrent VT in patients with dilated cardiomyopathies and ARVC.96100 In these patients, regions of scarring are often midmyocardial or epicardial and, therefore, ablation can be challenging. Epicardial access in these patients is possible using a percutaneous subxiphoid approach, in which a needle designed to enter potential spaces is passed into the pericardium, under fluoroscopic guidance, followed by a sheath advanced over a wire.101 The ablation catheter can then be introduced, and radiofrequency applied, although care is needed to avoid the coronary arteries and phrenic nerve.101104 The concept of preventive catheter ablation in patients with an ICD has been evaluated in two trials in the past 4 years. 76,77 Reddy et al. randomly assigned patients who received an ICD for secondary prevention of ventricular arrhythmias to catheter ablation or conventional therapy.76 Catheter ablation reduced the incidence of ventricular arrhythmias requiring ICD therapy from 33% to 12% (P = 0.007). In addition, despite the trial not being adequately powered to assess this outcome, a trend towards a reduction in mortality was reported.76 Kuck et al. randomly assigned patients presenting with hemodynamically stable monomorphic VT, prior myocardial infarction, and an LVEF 50% to catheter ablation plus an ICD or to an ICD alone.77 Patients receiving catheter ablation had a reduction in the number of appropriate
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ICD shocks (27% versus 47%) and a longer time to recurrence of VT (median 19 months versus 6 months).77 To date, no randomized trials comparing catheter ablation with antiarrhythmic therapy in the prevention of VT have been conducted.

PVCs and nonsustained VT PVCs and nonsustained VT are common among patients with structural heart disease. The mechanisms of these arrhythmias can be focal automaticity or triggered activity, as in patients without structural heart disease, or scar-related re-entry.105,106 Early studies suggested that frequent and repetitive ventricular ectopy, in association with a reduced LVEF, predicted an increased risk of sudden death among patients with myocardial infarction.107,108 However, more recently, this relationship has been questioned and the increased mortality risk is now thought to be related to the extent of structural heart disease. 109 Ambulatory monitoring of patients with heart failure has indicated that nonsustained ventricular arrhythmias do not seem to predict an increased risk of sudden death.110 In patients with nonischemic cardiomyopathy, determining whether PVCs are the cause of tachycardiamediated cardiomyopathy or the consequence of a primary cardiomyopathy is important. This distinction is essential, as the former condition can be reversible, particularly with the use of catheter ablation. Clinical clues that indicate tachycardia-mediated cardiomyopathy include very frequent PVCs (more than 10,000 per day, and often more than 20,000 per day 42,111,112), monomorphic PVCs arising from the outflow tract (LBBB or RBBB morphology with marked inferior axis), and a young, otherwise healthy, patient.113 Improvement in left ventricular function with suppression of PVCs, with either antiarrhythmic medication (such as amiodarone) or catheter ablation, confirms the diagnosis of tachycardia-mediated cardiomyopathy.
Management In most patients with structural heart disease, PVCs and nonsustained VT are asymptomatic. These arrhythmias do not reliably predict sudden death and no evidence exists that their suppression prolongs life. Therefore, treatment of these arrhythmias is not indicated. In a small proportion of patients, PVCs and nonsustained VT can produce symptoms and, in such cases, treatment with antiarrhythmic drug therapy or catheter ablation is appropriate. First-line antiarrhythmic therapy for symptomatic patients consists of -blockade. If this approach fails, amiodarone or sotalol are appropriate.3 Sarrazin et al. demonstrated that patients with prior myocardial infarction and frequent PVCs also have a component of tachycardia-mediated cardiomyopathy that can be reversible with catheter ablation.114 Assessment of the morphology of the PVCs or nonsustained VT should be performed to ensure that their site of origin is related to an area of scar, and not the result of a focal mechanism, such as would be the case with right ventricular outflow tract PVCs or VT, which are particularly amenable to catheter ablation.
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Polymorphic VT Polymorphic VT is defined by a changing QRS morphology from beat to beat, which can be sustainedoften requiring emergency cardioversionor self-limiting. Evaluation of the underlying substrate for polymorphic VT is important. Although the most common cause of polymorphic VT is acute ischemia, patients with other conditions such as long QT syndrome, Brugada syndrome, catecholaminergic polymorphic VT, and idiopathic VF can also present with polymorphic VT. Coronary angiography should be performed to exclude ischemia in patients with recurrent polymorphic VT. Correction of electrolyte abnormalities and stabilization of heart failure are also important. Intravenous administration of a -blocker is the treatment of choice for these patients3 and improves mortality in those with myocardial infarction and recurrent polymorphic VT.115 Amiodarone is also effective in controlling episodes of polymorphic VT.116,117 In patients with myocardial infarction, PVCs arising from the Purkinje system in the scar border zone can trigger episodes of polymorphic VT. Catheter ablation can be used to target these sites and suppress VT.118 Catheter ablation can also be successful in other substrates causing PVCs and polymorphic VT.119,120

Conclusions

Ventricular arrhythmias are the most common cause of sudden cardiac death. They usually occur in patients with structural heart disease, but are also occasionally seen in patients without demonstrable cardiac disease. A number of electrocardiographic criteria and algorithms exist to accurately diagnose VT. Patients with structurally normal hearts have benign prognoses and treatment is predominantly aimed at reducing symptoms. Most patients with scar-related VT receive an ICD for the prevention of sudden cardiac death; antiarrhythmic therapy can prevent VT recurrence but does not reduce mortality. Catheter ablation is useful in preventing VT recurrence, but research is still required to fully define its role in disease management. Currently several clinical trials are underway comparing catheter ablation with antiarrhythmic therapy, in particular amiodarone therapy, for the management of VT. The results of these studies will clarify the optimal management strategies for patients with VT. Clearly, research is required to determine why some patients develop VT and others remain arrhythmia-free. Ideally, preventing the development of ventricular scarring with improvements in the management of ischemic heart disease would be the preferable management strategy.
Review criteria
The PubMed database was searched to select articles for inclusion in this Review. Search terms included ventricular tachycardia, diagnosis, electrocardiogram, management, treatment, and catheter ablation. No date limit was set, but only fulltext articles in English were included.

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REVIEWS
1. Olshausen, K. V. et al. Sudden cardiac death while wearing a Holter monitor. Am. J. Cardiol. 67, 381386 (1991). Bays de Luna, A., Coumel, P . & Leclercq, J. F. Ambulatory sudden cardiac death: mechanisms of production of fatal arrhythmia on the basis of data from 157 cases. Am. Heart. J. 117, 151159 (1989). Zipes, D. P . et al. ACC/AHA/ESC 2006 Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: a report of the American College of Cardiology/American Heart Association Task Force and the European Society of Cardiology Committee for Practice Guidelines (writing committee to develop Guidelines for Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death): developed in collaboration with the European Heart Rhythm Association and the Heart Rhythm Society. Circulation 114, e385e484 (2006). Vereckei, A., Duray, G., S zensi, G., Altemose, G. T. & Miller, J. M. Application of a new algorithm in the differential diagnosis of wide QRS complex tachycardia. Eur. Heart J. 28, 589600 (2007). Baerman, J. M., Morady, F., DiCarlo, L. A. Jr & de Buitleir, M. Differentiation of ventricular tachycardia from supraventricular tachycardia with aberration: value of the clinical history. Ann. Emerg. Med. 16, 4043 (1987). Garratt, C. J. et al. Value of physical signs in the diagnosis of ventricular tachycardia. Circulation 90, 31033107 (1994). Willems, J. L. et al. Criteria for intraventricular conduction disturbances and pre-excitation. World Health Organizational/International Society and Federation for Cardiology Task Force Ad Hoc. J. Am. Coll. Cardiol. 5, 12611275 (1985). Griffith, M. J., Garratt, C. J., Mounsey, P .& Camm, A. J. Ventricular tachycardia as default diagnosis in broad complex tachycardia. Lancet 343, 386388 (1994). Vereckei, A., Duray, G., S zensi, G., Altemose, G. T. & Miller, J. M. New algorithm using only lead aVR for differential diagnosis of wide QRS complex tachycardia. Heart Rhythm 5, 8998 (2008). Akhtar, M., Shenasa, M., Jazayeri, M., Caceres, J. & Tchou, P . J. Wide QRS complex tachycardia. Reappraisal of a common clinical problem. Ann. Intern. Med. 109, 905912 (1988). Wellens, H. J., Br, F. W. & Lie, K. I. The value of the electrocardiogram in the differential diagnosis of a tachycardia with a widened QRS complex. Am. J. Med. 64, 2733 (1978). Brugada, P ., Brugada, J., Mont, L., Smeets, J. & Andries, E. W. A new approach to the differential diagnosis of a regular tachycardia with a wide QRS complex. Circulation 83, 16491659 (1991). Vandepol, C. J. et al. Incidence and clinical significance of induced ventricular tachycardia. Am. J. Cardiol. 45, 725731 (1980). Lerman, B. B. et al. Mechanism of repetitive monomorphic ventricular tachycardia. Circulation 92, 421429 (1995). Blomstrom-Lundqvist, C., Beckman-Suurkula, M., Wallentin, I., Jonsson, R. & Olsson, S. B. Ventricular dimensions and wall motion assessed by echocardiography in patients with arrhythmogenic right ventricular dysplasia. Eur. Heart J. 9, 12911302 (1988). Bogun, F. M. et al. Delayed-enhanced magnetic resonance imaging in nonischemic cardiomyopathy: utility for identifying the ventricular arrhythmia substrate. J. Am. Coll. Cardiol. 53, 11381145 (2009). Yan, A. T. et al. Characterization of the peri-infarct zone by contrast-enhanced cardiac magnetic resonance imaging is a powerful predictor of post-myocardial infarction mortality. Circulation 114, 3239 (2006). Marcus, F. I. et al. Diagnosis of arrhythmogenic right ventricular cardiomyopathy/dysplasia: proposed modification of the task force criteria. Circulation 121, 15331541 (2010). Sacher, F. et al. Ventricular tachycardia ablation. Evolution of patients and procedures over 8 years. Circ. Arrhythm. Electrophysiol. 1, 153161 (2008). Badhwar, N. & Scheinman, M. M. Idiopathic ventricular tachycardia: diagnosis and management. Curr. Probl. Cardiol. 32, 743 (2007). Buxton, A. E. et al. Right ventricular tachycardia: clinical and electrophysiologic characteristics. Circulation 68, 917927 (1983). Mont, L. et al. Clinical and electrophysiologic characteristics of exercise-related idiopathic ventricular tachycardia. Am. J. Cardiol. 68, 897900 (1991). Crawford, T. et al. Ventricular arrhythmias originating from papillary muscles in the right ventricle. Heart Rhythm 7, 725730 (2010). Good, E. et al. Ventricular arrhythmias originating from a papillary muscle in patients without prior infarction: a comparison with fascicular arrhythmias. Heart Rhythm 5, 15301537 (2008). Yamada, T. et al. Idiopathic focal ventricular arrhythmias originating from the anterior papillary muscle in the left ventricle. J. Cardiovasc. Electrophysiol. 20, 866872 (2009). Doppalapudi, H. et al. Ventricular tachycardia originating from the posterior papillary muscle in the left ventricle: a distinct clinical syndrome. Circ. Arrhythm. Electrophysiol. 1, 2329 (2008). McKenna, W. J. et al. Diagnosis of arrhythmogenic right ventricular dysplasia/cardiomyopathy. Task Force of the Working Group Myocardial and Pericardial Disease of the European Society of Cardiology and of the Scientific Council on Cardiomyopathies of the International Society and Federation of Cardiology. Br. Heart J. 71, 215218 (1994). Lerman, B. B. Mechanism of outflow tract tachycardia. Heart Rhythm 4, 973976 (2007). Lerman, B. B., Belardinelli, L., West, G. A., Berne, R. M. & DiMarco, J. P . Adenosine-sensitive ventricular tachycardia: evidence suggesting cyclic AMP-mediated triggered activity. Circulation 74, 270280 (1986). Gaita, F. et al. Long-term follow-up of right ventricular monomorphic extrasystoles. J. Am. Coll. Cardiol. 38, 364370 (2001). Lemery, R. et al. Nonischemic ventricular tachycardia. Clinical course and long-term follow-up in patients without clinically overt heart disease. Circulation 79, 990999 (1989). Kim, R. J. et al. Clinical and electrophysiological spectrum of idiopathic ventricular outflow tract arrhythmias. J. Am. Coll. Cardiol. 49, 20352043 (2007). Buxton, A. E. et al. Right ventricular tachycardia: clinical and electrophysiologic characteristics. Circulation 68, 917927 (1983). Gill, J. S., Ward, D. E. & Camm, A. J. Comparison of verapamil and diltiazem in the suppression of idiopathic ventricular tachycardia. Pacing Clin. Electrophysiol. 15, 21222126 (1992). Gill, J. S., Mehta, D., Ward, D. E. & Camm, A. J. Efficacy of flecainide, sotalol, and verapamil in the treatment of right ventricular tachycardia in patients without overt cardiac abnormality. Br. Heart J. 68, 392397 (1992). Gill, J. S., Blaszyk, K., Ward, D. E. & Camm, A. J. Verapamil for the suppression of idiopathic ventricular tachycardia of left bundle branch block-like morphology. Am. Heart J. 126, 11261133 (1993). Rahilly, G. T. et al. Clinical and electrophysiologic findings in patients with repetitive monomorphic ventricular tachycardia and otherwise normal electrocardiogram. Am. J. Cardiol. 50, 459468 (1982). Goy, J. J. et al. Ten-years follow-up of 20 patients with idiopathic ventricular tachycardia. Pacing Clin. Electrophysiol. 13, 11421147 (1990). Joshi, S. & Wilber, D. J. Ablation of idiopathic right ventricular outflow tract tachycardia: current perspectives. J. Cardiovasc. Electrophysiol. 16 (Suppl. 1), S52S58 (2005). Scheinman, M. M. & Huang, S. The 1998 NASPE prospective catheter ablation registry. Pacing Clin. Electrophysiol. 23, 10201028 (2000). Seiler, J., Lee, J. C., Roberts-Thomson, K. C. & Stevenson, W. G. Intracardiac echocardiography guided catheter ablation of incessant ventricular tachycardia from the posterior papillary muscle causing tachycardia-mediated cardiomyopathy. Heart Rhythm 6, 389392 (2009). Yarlagadda, R. K. et al. Reversal of cardiomyopathy in patients with repetitive monomorphic ventricular ectopy originating from the right ventricular outflow tract. Circulation 112, 10921097 (2005). Bubien, R. S., Knotts-Dolson, S. M., Plumb, V. J. & Kay, G. N. Effect of radiofrequency catheter ablation on health-related quality of life and activities of daily living in patients with recurrent arrhythmias. Circulation 94, 15851591 (1996). Ohe, T. et al. Long-term outcome of verapamilsensitive sustained left ventricular tachycardia in patients without structural heart disease. J. Am. Coll. Cardiol. 25, 5458 (1995). German, L. D., Packer, D. L., Bardy, G. H. & Gallagher, J. J. Ventricular tachycardia induced by atrial stimulation in patients without symptomatic cardiac disease. Am. J. Cardiol. 52, 12021207 (1983). Nogami, A. et al. Demonstration of diastolic and presystolic Purkinje potentials as critical potentials in a macroreentry circuit of verapamilsensitive idiopathic left ventricular tachycardia. J. Am. Coll. Cardiol. 36, 811823 (2000). Maruyama, M., Tadera, T., Miyamoto, S. & Ino, T. Demonstration of the reentrant circuit of verapamil-sensitive idiopathic left ventricular tachycardia: direct evidence for macroreentry as the underlying mechanism. J. Cardiovasc. Electrophysiol. 12, 968972 (2001). Nogami, A. et al. Verapamil-sensitive left anterior fascicular ventricular tachycardia: results of radiofrequency ablation in six patients. J. Cardiovasc. Electrophysiol. 9, 12691278 (1998). Griffith, M. J., Garratt, C. J., Rowland, E., Ward, D. E. & Camm, A. J. Effects of intravenous adenosine on verapamil-sensitive idiopathic ventricular tachycardia. Am. J. Cardiol. 73, 759764 (1994). Ohe, T. et al. Idiopathic sustained left ventricular tachycardia: clinical and electrophysiologic characteristics. Circulation 77, 560568 (1988). Kottkamp, H. et al. Idiopathic left ventricular tachycardia: new insights into electrophysiological characteristics and radiofrequency catheter ablation. Pacing Clin. Electrophysiol. 18, 12851297 (1995).

17.

2.

36.

18.

3.

37.

19.

38.

20.

39.

21.

40.

4.

22.

41.

23.

5.

24.

42.

6.

25.

7.

43.

26.

44.

8.

27.

45.

9.

46.

10.

28. 29.

11.

47.

12.

30.

48.

31.

13.

32.

49.

14.

15.

33.

50.

34.

51.

16.

35.

NATURE REVIEWS | CARDIOLOGY

2011 Macmillan Publishers Limited. All rights reserved

ADVANCE ONLINE PUBLICATION | 9

REVIEWS
52. Nakagawa, H. et al. Radiofrequency catheter ablation of idiopathic left ventricular tachycardia guided by a Purkinje potential. Circulation 88, 26072617 (1993). 53. Thakur, R. K. et al. Anatomic substrate for idiopathic left ventricular tachycardia. Circulation 93, 497501 (1996). 54. de Bakker, J. M. et al. Slow conduction in the infarcted human heart. Zigzag course of activation. Circulation 88, 915926 (1993). 55. Peters, N. S., Coromilas, J., Severs, N. J. & Wit, A. L. Disturbed connexin43 gap junction distribution correlates with the location of reentrant circuits in the epicardial border zone of healing canine infarcts that cause ventricular tachycardia. Circulation 95, 988996 (1997). 56. Haqqani, H. M. et al. Fundamental differences in electrophysiologic and electroanatomic substrate between ischemic cardiomyopathy patients with and without clinical ventricular tachycardia. J. Am. Coll. Cardiol. 54, 166173 (2009). 57. Calkins, H. et al. Catheter ablation of ventricular tachycardia in patients with structural heart disease using cooled radiofrequency energy: results of a prospective multicenter study. Cooled RF Multi Center Investigators Group. J. Am. Coll. Cardiol. 35, 19051914 (2000). 58. Stevenson, W. G. et al. Irrigated radiofrequency catheter ablation guided by electroanatomic mapping for recurrent ventricular tachycardia after myocardial infarction: the multicenter thermocool ventricular tachycardia ablation trial. Circulation 118, 27732782 (2008). 59. Caceres, J. et al. Sustained bundle branch reentry as a mechanism of clinical tachycardia. Circulation 79, 256270 (1989). 60. Blanck, Z. et al. Bundle branch reentrant ventricular tachycardia: cumulative experience in 48 patients. J. Cardiovasc. Electrophysiol. 4, 253262 (1993). 61. Cohen, T. J. et al. Radiofrequency catheter ablation for treatment of bundle branch reentrant ventricular tachycardia: results and long-term follow-up. J. Am. Coll. Cardiol. 18, 17671773 (1991). 62. Moss, A. J. et al. for the Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction. N. Engl. J. Med. 346, 877883 (2002). 63. Bardy, G. H. et al. for the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverterdefibrillator for congestive heart failure. N. Engl. J. Med. 352, 225237 (2005). 64. Nasir, N. Jr, Taylor, A., Doyle, T. K. & Pacifico, A. Evaluation of intravenous lidocaine for the termination of sustained monomorphic ventricular tachycardia in patients with coronary artery disease with or without healed myocardial infarction. Am. J. Cardiol. 74, 11831186 (1994). 65. Gorgels, A. P . et al. Comparison of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Am. J. Cardiol. 78, 4346 (1996). 66. Ho, D. S., Zecchin, R. P ., Richards, D. A., Uther, J. B. & Ross, D. L. Double-blind trial of lignocaine versus sotalol for acute termination of spontaneous sustained ventricular tachycardia. Lancet 344, 1823 (1994). 67. Somberg, J. C. et al. for the Amio-Aqueous Investigators. Intravenous lidocaine versus intravenous amiodarone (in a new aqueous formulation) for incessant ventricular tachycardia. Am. J. Cardiol. 90, 853859 (2002). 68. Marill, K. A. et al. Amiodarone or procainamide for the termination of sustained stable ventricular tachycardia: an historical multicenter comparison. Acad. Emerg. Med. 17, 297306 (2010). Komura, S. et al. Efficacy of procainamide and lidocaine in terminating sustained monomorphic ventricular tachycardia. Circ. J. 74, 864869 (2010). Mitchell, L. B., Wyse, D. G., Gillis, A. M. & Duff, H. J. Electropharmacology of amiodarone therapy initiation. Time courses of onset of electrophysiologic and antiarrhythmic effects. Circulation 80, 3442 (1989). Kulakowski, P ., Karczmarewicz, S., Karpi nski, G., Soszy nska, M. & Ceremuzy nski, L. Effects of intravenous amiodarone on ventricular refractoriness, intraventricular conduction, and ventricular tachycardia induction. Europace 2, 207215 (2000). Tomlinson, D. R., Cherian, P ., Betts, T. R. & Bashir, Y. Intravenous amiodarone for the pharmacological termination of hemodynamically-tolerated sustained ventricular tachycardia: is bolus dose amiodarone an appropriate first-line treatment? Emerg. Med. J. 25, 1518 (2008). Manz, M., Mletzko, R., Jung, W. & Lderitz, B. Electrophysiological and hemodynamic effects of lidocaine and ajmaline in the management of sustained ventricular tachycardia. Eur. Heart J. 13, 11231128 (1992). Camm, J., Ward, D., Washington, H. G. & Spurrell, R. A. Intravenous disopyramide phosphate and ventricular overdrive pacing in the termination of paroxysmal ventricular tachycardia. Pacing Clin. Electrophysiol. 2, 395402 (1979). Oldroyd, K. G., Rankin, A. C., Rae, A. P .& Cobbe, S. M. Pacing termination of spontaneous ventricular tachycardia in the coronary care unit. Int. J. Cardiol. 36, 223226 (1992). Reddy, V. Y. et al. Prophylactic catheter ablation for the prevention of defibrillator therapy. N. Engl. J. Med. 357, 26572665 (2007). Kuck, K. H. et al. Catheter ablation of stable ventricular tachycardia before defibrillator implantation in patients with coronary heart disease (VTACH): a multicenter randomised controlled trial. Lancet 375, 3140 (2010). Connolly, S. J. et al. Comparison of beta-blockers, amiodarone plus beta-blockers, or sotalol for prevention of shocks from implantable cardioverter defibrillators: the OPTIC Study: a randomized trial. JAMA 295, 165171 (2006). Mont, L. et al. Arrhythmia recurrence in patients with a healed myocardial infarction who received an implantable defibrillator: analysis according to the clinical presentation. J. Am. Coll. Cardiol. 34, 351357 (1999). Goldstein, S. et al. Predictive survival models for resuscitated victims of out-of-hospital cardiac arrest with coronary heart disease. Circulation 71, 873880 (1985). Baum, R. S., Alvarez, H. 3rd & Cobb, L. A. Survival after resuscitation from out-of-hospital ventricular fibrillation. Circulation 50, 12311235 (1974). The Antiarrhythmics versus Implantable Defibrillators (AVID) Investigators. A comparison of antiarrhythmic-drug therapy with implantable defibrillators in patients resuscitated from nearfatal ventricular arrhythmias. N. Engl. J. Med. 337, 15761583 (1997). Poole, J. E. et al. Prognostic importance of defibrillator shocks in patients with heart failure. N. Engl. J. Med. 359, 10091017 (2008). Moss, A. J. et al. Long-term clinical course of patients after termination of ventricular tachyarrhythmia by an implanted defibrillator. Circulation 110, 37603765 (2004). 85. Yusuf, S., Peto, R., Lewis, J., Collins, R. & Sleight, P . Beta blockade during and after myocardial infarction: an overview of the randomized trials. Prog. Cardiovasc. Dis. 27, 335371 (1985). 86. Hjalmarson, A. Effects of beta blockade on sudden cardiac death during acute myocardial infarction and the postinfarction period. Am. J. Cardiol. 80, 35J39J (1997). 87. Pfeffer, M. A. et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N. Engl. J. Med. 327, 669677 (1992). 88. The SOLVD Investigators. Effect of enalapril on mortality and the development of heart failure in asymptomatic patients with reduced left ventricular ejection fractions. N. Engl. J. Med. 327, 685691 (1992). 89. Kuck, K. H., Cappato, R., Siebels, J. & Ruppel, R. Randomized comparison of antiarrhythmic drug therapy with implantable defibrillators in patients resuscitated from cardiac arrest: the Cardiac Arrest Study Hamburg (CASH). Circulation 102, 748754 (2000). 90. The Cardiac Arrhythmia Suppression Trial (CAST) Investigators. Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction. N. Engl. J. Med. 321, 406412 (1989). 91. Khlkamp, V., Mewis, C., Mermi, J., Bosch, R. F. & Seipel, L. Suppression of sustained ventricular tachyarrhythmias: a comparison of D,L-sotalol with no antiarrhythmic drug treatment. J. Am. Coll. Cardiol. 33, 4652 (1999). 92. Whitford, E. G. et al. Long-term efficacy of mexiletine alone and in combination with class Ia antiarrhythmic drugs for refractory ventricular arrhythmias. Am. Heart J. 115, 360366 (1988). 93. Ravid, S., Lampert, S. & Graboys, T. B. Effect of the combination of low-dose mexiletine and metoprolol on ventricular arrhythmia. Clin. Cardiol. 14, 951955 (1991). 94. Mason, J. W. A comparison of electrophysiologic testing with Holter monitoring to predict antiarrhythmic-drug efficacy for ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators. N. Engl. J. Med. 329, 445451 (1993). 95. Stevenson, W. G. et al. Identification of reentry circuit sites during catheter mapping and radiofrequency ablation of ventricular tachycardia late after myocardial infarction. Circulation 88, 16471670 (1993). 96. Soejima, K. et al. Endocardial and epicardial radiofrequency ablation of ventricular tachycardia associated with dilated cardiomyopathy: the importance of low-voltage scars. J. Am. Coll. Cardiol. 43, 18341842 (2004). 97. Hsia, H. H., Callans, D. J. & Marchlinski, F. E. Characterization of endocardial electrophysiological substrate in patients with nonischemic cardiomyopathy and monomorphic ventricular tachycardia. Circulation 108, 704710 (2003). 98. Cano, O. et al. Electroanatomic substrate and ablation outcome for suspected epicardial ventricular tachycardia in left ventricular nonischemic cardiomyopathy. J. Am. Coll. Cardiol. 54, 799808 (2009). 99. Garcia, F. C., Bazan, V., Zado, E. S., Ren, J. F. & Marchlinski, F. E. Epicardial substrate and outcome with epicardial ablation of ventricular tachycardia in arrhythmogenic right ventricular

69.

70.

71.

72.

73.

74.

75.

76.

77.

78.

79.

80.

81.

82.

83.

84.

10 | ADVANCE ONLINE PUBLICATION

2011 Macmillan Publishers Limited. All rights reserved

www.nature.com/nrcardio

REVIEWS
cardiomyopathy/dysplasia. Circulation 120, 366375 (2009). 100. Ellison, K. E., Friedman, P . L., Ganz, L. I. & Stevenson, W. G. Entrainment mapping and radiofrequency catheter ablation of ventricular tachycardia in right ventricular dysplasia. J. Am. Coll. Cardiol. 32, 724728 (1998). 101. Sosa, E., Scanavacca, M., dAvila, A. & Pilleggi, F. A new technique to perform epicardial mapping in the electrophysiology laboratory. J. Cardiovasc. Electrophysiol. 7, 531536 (1996). 102. Sosa, E., Scanavacca, M. & dAvila, A. Transthoracic epicardial catheter ablation to treat recurrent ventricular tachycardia. Curr. Cardiol. Rep. 3, 451458 (2001). 103. Roberts-Thomson, K. C. et al. Percutaneous access of the epicardial space for mapping ventricular and supraventricular arrhythmias in patients with and without prior cardiac surgery. J. Cardiovasc. Electrophysiol. 21, 406411 (2010). 104. Roberts-Thomson, K. C. et al. Coronary artery injury due to catheter ablation in adults: presentations and outcomes. Circulation 120, 14651473 (2009). 105. Bogun, F. et al. Relationship of frequent postinfarction premature ventricular complexes to the reentry circuit of scar-related ventricular tachycardia. Heart Rhythm 5, 367374 (2008). 106. Sarrazin, J. F. et al. Mapping and ablation of frequent post-infarction premature ventricular complexes. J. Cardiovasc. Electrophysiol. 21, 10021008 (2010). 107. Bigger, J. T., Jr, Fleiss, J. L., Kleiger, R., Miller, J. P . & Rolnitzky, L. M. The relationships among ventricular arrhythmias, left ventricular dysfunction, and mortality in the 2 years after myocardial infarction. Circulation 69, 250258 (1984). 108. Ruberman, W. et al. Ventricular premature complexes and sudden death after myocardial infarction. Circulation 64, 297305 (1981). 109. Huikuri, H. V. et al. Prediction of sudden cardiac death: appraisal of the studies and methods assessing the risk of sudden arrhythmic death. Circulation 108, 110115 (2003). 110. Teerlink, J. R. et al. Ambulatory ventricular arrhythmias in patients with heart failure do not specifically predict an increased risk of sudden death. PROMISE (Prospective Randomized Milrinone Survival Evaluation) Investigators. Circulation 101, 4046 (2000). 111. Takemoto, M. et al. Radiofrequency catheter ablation of premature ventricular complexes from right ventricular outflow tract improves left ventricular dilation and clinical status in patients without structural heart disease. J. Am. Coll. Cardiol. 45, 12591265 (2005). 112. Baman, T. S. et al. Relationship between burden of premature ventricular complexes and left ventricular function. Heart Rhythm 7, 865869 (2010). 113. Sheldon, S. H., Gard, J. J. & Asirvatham, S. J. Premature ventricular contractions and nonsustained ventricular tachycardia: association with sudden cardiac death, risk stratification, and management strategies. Indian Pacing Electrophysiol. J. 10, 357371 (2010). 114. Sarrazin, J. F. et al. Impact of radiofrequency ablation of frequent post-infarction premature ventricular complexes on left ventricular ejection fraction. Heart Rhythm 6, 15431549 (2009). 115. Nademanee, K., Taylor, R., Bailey, W. E., Rieders, D. E. & Kosar, E. M. Treating electrical storm: sympathetic blockade versus advanced cardiac life support-guided therapy. Circulation 102, 742747 (2000). 116. Kowey, P . R. et al. Randomized, double-blind comparison of intravenous amiodarone and bretylium in the treatment of patients with recurrent, hemodynamically destabilizing ventricular tachycardia or fibrillation. The Intravenous Amiodarone Multicenter Investigators Group. Circulation 92, 32553263 (1995). 117. Kowey, P . R., Marinchak, R. A., Rials, S. J. & Bharucha, D. B. Intravenous antiarrhythmic therapy in the acute control of in-hospital destabilizing ventricular tachycardia and fibrillation. Am. J. Cardiol. 84, 46R51R (1999). 118. Szumowski, L. et al. Mapping and ablation of polymorphic ventricular tachycardia after myocardial infarction. J. Am. Coll. Cardiol. 44, 17001706 (2004). 119. Hassaguerre, M. et al. Mapping and ablation of idiopathic ventricular fibrillation. Circulation 106, 962967 (2002). 120. Hassaguerre, M. et al. Mapping and ablation of ventricular fibrillation associated with long-QT and Brugada syndromes. Circulation 108, 925928 (2003). Acknowledgments K. C. Roberts-Thomson and P . Sanders are supported by the National Heart Foundation of Australia. Author contributions K. C. Roberts-Thomson researched data for the article. All the authors contributed to the discussion of content, wrote the article, and reviewed/edited the manuscript before submission and after peer-review.

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