European Heart Journal (1992) 13 (Supplement F), 44-52
How to prescribe and manage antiarrhythmic drug therapy A. J. CAMM AND D. KATRITSIS
Department of Cardiological Sciences, St George's Hospital Medical School, London, U.K.
Summary
The pharmacological approach is the comer-stone of therapy for arrhythmia because it is non-invasive, convenient and widely available. However, the indications for antiarrhythmic therapy in general, as well as the indications for drug therapy as opposed to non-pharmacological therapeutic methods, are far from clearly defined. Among the existing antiarrhythmic drugs, clear reduction of mortality due to arrhythmia has been shown definitively only with beta-blocking agents and possibly with amiodarone. PREDICTION OF EFFICACY
Selection of the appropriate antiarrhythmic drug for management of supra ventricular arrhythmia is potentially rational since it can, in part, be predicted from our knowledge of the mechanism of the arrhythmia and the tissuespecificity of the drugs. Thus, agents prolonging the refractoriness of the atrio-ventricular (AV) node are selected for the treatment of reentrant arrhythmias involving the node, whereas atrio-ventricular reentrant arrhythmias involving accessory pathways can be managed with drugs which affect other parts of the macrocircuit which supports the arrhythmia. Ventricular tachyarrhythmias are difficult to treat and the drug selection is more empirical. Drugs such as amiodarone or sotalol are the first choice agents for this purpose. Specific drug therapy can be guided by invasive electrophysiology studies, Holter monitoring and exercise testing. In centres with electrophysiology facilities, programmed electrical stimulation is currently used for risk stratification of arrhythmia patients and for guidance of drug selection and treatment efficacy in patients with monomorphic ventricular tachycardia and in survivors of ventricular fibrillation (VF) with preserved left ventricular (LV) function (ejection fraction (EF) >30%). Although limited data from one randomized study have suggested that programmed electrical stimulation is superior to non-invasive methods, such as electrocardiographic monitoring, for predicting treatment efficacy, this issue is currently under further investigation. Furthermore, the time limitations of these predictions, i.e. the history of arrhythmias treated by drugs selected by the invasive or the non-invasive approach, is entirely unknown. Signal averaged electrocardiography for detection of late potentials and assessment of cardiac autonomic tone by means of heart rate variability analysis are also being evaluated. It has been suggested that drug level Conespondcnct: Profeisor A. John Camm, Department of Cardiological Sciences, St George's Hospital Medical School, London, U.K 0195-668X/92/OF0044 + 09 S08.00/0
measurement may be essential formonitoring antiarrhythmic therapy. Alternatively, ensuring that the electrocardiographic response to antiarrhythmic drug therapy is present may be a better approach. SAFETY MONITORING
One of the major problems of almost all antiarrhythmic drugs is the narrow therapeutic-toxic margin they display in clinical practice. The most important, life-threatening side effect of antiarrhythmic drugs is pro-arrhythmia, which gives rise to considerable concern about their clinical use. It is not possible to eliminate the risk of proarrhythmia, but patient monitoring with electrolyte measurement, drug level assays, Holter recordings, exercise testing and electrophysiological reassessment may reduce this possibility. The immediate aim of antiarrhythmic therapy is to suppress the arrhythmia, but its overall beneficial effect can only be confirmed by demonstration of a reduction in the morbidity and mortality associated with the arrhythmia under treatment. The institution of antiarrhythmic therapy should be initiated in seriously symptomatic or life-threatening arrhythmias after careful consideration of the benefit-risk ratio. Introduction
During the last decade, exciting progress has been made in the treatment of arrhythmias, not only by development of new drugs, but also by the introduction of alternative methods of treatment, such as implantable devices, and catheter or surgical ablation1'"41. The pharmacological approach remains the corner-stone of therapy. It may not be always the cheapest or the most efficient mode of treatment15' but it is non-invasive, more convenient and widely available. However, despite the long use of numerous antiarrhythmic agents, some questions still remain without a definitive answer: what are the specific indications for these drugs, on what grounds should they be selected for each case and how should the patient be monitored during such treatment? Indications for therapy
The indications for antiarrhythmic therapy, in general, are far from clearly defined, but most authorities would agree that symptomatic or life-threatening arrhythmias deserve specific treatment'2"41. The advent of catheter and surgical ablation techniques for a curative treatment of arrhythmias has made this modality, whenever feasible, the treatment of choice for the management of such > 1992 The European Society of Cardiology
•s-
Managing antiarrhythmic drug therapy 45
patients. When radical treatment is not possible or is accompanied by a high operative risk, such arrhythmias should be treated with drugs, implantable devices or both. However, whether such therapy improves mortality and reduces the incidence of cardiac sudden death and how drug therapy, in particular, compares with alternative therapies is not yet known. In addition, the choice of the initial agent for a particular arrhythmia remains largely empiric. Choice of agent—prediction of efficacy SUPRAVENTRICULAR AND ATRIOVENTRICULAR (USING ACCESSORY PATHWAYS) ARRHYTHMIAS
Selection of the appropriate drug for supraventricular arrhythmias may be quite logical since efficacy can be predicted from a knowledge of the mechanism of the arrhythmia and the tissue-specificity of the drugs. Thus, agents prolonging the refractoriness of the AV node (calcium antagonists, beta-blockers and digoxin) are selected for the treatment of reentrant arrhythmias involving the node, whereas atrioventricular reentrant arrhythmias involving accessory pathways can be interrupted either at the node or the pathway (classes la, Ic and III)141. In chronic atrial fibrillation, therapy is usually aimed at the control of the ventricular response with AV nodal blocking agents, whereas for paroxysmal atrial fibrillation (AF) drugs stabilizing the atrium (such as class la, Ic and III) are used'61. For paroxysmal atrial flutter, no entirely satisfactory drug exists but in our experience sotalol[7] is a useful agent for this purpose. In the absence of ventricular disease, the risk of therapy with class Ic agents may be considerably less than found in the CAST population181. However, reservations have been recently expressed about the safety of flecainide as well as quinidine in the setting of atrial fibrillation, and the matter probably needs further consideration and study. The administration of flecainide in patients with chronic or paroxysmal atrial fibrillation has been found to be complicated by life-threatening ventricular arrhythmias'9"121 and this pro-arrhythmic effect might be associated with exercise1"1. Falk'"1 reported on three such patients receiving flecainide for chronic or paroxysmal atrial fibrillation. Two of them developed ventricular arrhythmias during peak exercise without any previous symptoms or evidence from Holter monitoring of sustained ventricular tachycardia. A meta-analysis of clinical studies comparing quinidine with placebo for long-term prevention of atrial fibrillation after cardioversion from this arrhythmia showed an increased mortality in patients who were treated with the drug*131. Although this report has included only part of the available data on the subject, it questions the role of quinidine in the long-term treatment of this patient group. These reports indicate the need for a more thorough assessment of the safety profile of class I drugs. Supraventricular arrhythmias generally have a good prognosis, especially when associated with structurally normal hearts, but they may all result in sudden cardiac death'14151 and some form of treatment may be necessary not only for the highly symptomatic cases. The efficacy of
the proposed drugs can be assessed in the electrophysiology laboratory by demonstrating lack of inducibility of the reentrant arrhythmia and, in the case of atrioventricular reentrant arrhythmias, by additional measurement of the achieved prolongation of refractoriness of the accessory pathway1'5'161. This usually requires invasive electrophysiology studies: alternatively, transoesophageal pacing can be used, but this technique may at times be more uncomfortable for the patient than the insertion of intracardiac electrodes. In atrial fibrillation, electrocardiographic monitoring and symptomatic improvement are the only guides for assessing treatment efficacy. Although ECG monitoring and exercise testing can be used for the long-term follow-up of these patients'41, no data exist to validate the clinical benefits of this practice. Unfortunately, the long-term management and follow-up of these patients is based on empiricism and the clinician's judgement for every individual case. VENTRICULAR TACHYARRHYTHMIAS
The proper management of ventricular arrhythmias represents a serious challenge for the clinical cardiologist and the available data do not allow answers to several important questions. Sudden cardiac death, which is probably caused by ventricular arrhythmias in the majority of cases'17'181, remains a major health problem despite the widespread use of antiarrhythmic drugs. The patient with compromised LV function and sustained ventricular tachycardia or VF has a sudden death rate of approximately 20 to 30% per year if treated empirically"9"231. With the use of electrophysiology- or ECG monitoringguided drug therapy and possibly amiodarone (as well as implantable defibrillators) the sudden death rate may be reduced to 5-10% per year123"271. Thus, we can project that careful therapeutic intervention with drugs may reduce the incidence of sudden death in patients with malignant arrhythmias, but definitive evidence based on controlled trials is missing. As yet, with the exception of beta-blockers in post-infarct patients'281 (and, perhaps, amiodarone in hypertrophic cardiomyopathy'291 and post-infarct patients'301), no convincing evidence has been presented that suppression of spontaneously occurring arrhythmias by antiarrhythmic drugs decreases the incidence of arrhythmic death. Furthermore, in the case of nonsustained ventricular tachycardia (VT) or asymptomatic ventricular ectopic activity in the post-infarction patient, there is enormous controversy regarding the correct management'311. Ventricular tachyarrhythmias are more difficult to treat compared with supraventricular arrhythmias. When drug therapy is chosen, the physician has two options: empirical or guided therapy. For the empirical option, drugs such as amiodarone or sotalol appear to be the first choice'32"341, having demonstrated maximum efficacy in the comparative published series. Specific drug therapy can be guided by invasive studies, such as programmed electrical stimulation, or non-invasive ones, such as Holter monitoring and exercise testing. The non-invasive approach begins with determination of the frequency and complexity of the ventricular
46 A.J. Camm andD. Katritsis
arrhythmia in a drug-free state by means of ambulatory electrocardiographic monitoring and exercise testing. Successful therapy is then defined by suppression of this spontaneous arrhythmia'24'35-'61. Graboys et a/.'241 studied 123 cardiac arrest survivors by means of 48-h Holter monitoring (100 patients) and exercise testing (60 patients). Suppression of non-sustained runs of VT or R-on-T ventricular premature beats (VPBs) identified on Holter monitoring or during exercise testing, was accompanied by reduced mortality (annual incidence of sudden death 2-3% in patients with effective therapy vs 43-6% in patients with ineffective therapy). This study suffered from several methodological problems, the most important of which is the adoption of the so-called 'fail-safe' programme of drug protection, i.e. the administration of an additional antiarrhythmic drug to the identified effective agent. The invasive approach employs programmed electrical stimulation (PES) in a drug-free state that induces the patient's ventricular arrhythmia. Successful therapy is then defined by suppression of the inducibility of the tachycardia'37"40'. Sustained monomorphic VT can be induced by PES in a large majority of patients who present with this arrhythmia, the rate of inducibility being more than 90% in patients with ischaemic heart disease (IHD) but somewhat lower in patients with cardiomyopathy or normal heart VT14142-31'. In survivors of cardiac arrest, PES results in the induction of sustained ventricular tachycardia, polymorphic VT/VF in up to 80% of patients'4344'. In sudden cardiac death survivors, polymorphic VT/VF are accepted as end-points to guide the selection of antiarrhythmic therapy122'. Although there is a recognised day-to-day variability in the mode of induction, rate and electrocardiographic morphology of induced VT in up to 40% of patients'451, PES allows the selection of a drug that prevents induction of the clinical arrhythmia in approximately 20-50% of patients with ventricular tachyarrhythmias'42'46'481. These patients are at a significantly lower risk for recurrent spontaneous ventricular tachycardia and sudden death than patients in whom a suppressive drug cannot be identified'21 •2Z40'49'. Retrospective analyses'50-511 and concordance studies'5"3' have suggested that the invasive approach predicts the prevention of VT recurrence better than the non-invasive approach. There is also evidence from the one randomized study so far available, that therapy selected by electrophysiological testing can prevent recurrences of VT better than that selected by Holter monitoring and exercise testing (Fig. I)'54'. Significant differences were also observed when amiodarone recipients were excluded. Unfortunately, the number of enrolled patients was rather small (57 patients) for the extraction of defined conclusions. The ESVEM study (Electrophysiologic Study Versus Electrocardiographic Monitoring)'551, a large multicentre trial, addresses the same question (Fig. 2). Preliminary analysis of the results has shown no significant differences between the invasive and non-invasive groups in terms of cardiac death and arrhythmia recurrence over a 4 year follow-up, although at 1 -5 years, there was a trend for less arrhythmia recurrences in the PES group (Fig. 2).
oo Holler PES Two-year follow-up
Figure 1 Recurrences,of tachyarrhythmia and sudden death in patients treated by the invasive and non-invasive approaches in the Calgary study (Mitchell el a/.|M|). 0 = arrhythmia /> = 002; • = sudden death /> = NS.
We believe that the two approaches should be considered complementary rather than competitive. The information derived from them is not comparable: ECG monitoring registers the effect of an intervention on VPBs or a spontaneously occurring arrhythmia, whereas PES induces the clinical arrhythmia and gives information on the effect on its substrate. One of the inclusion criteria for the ESVEM, for example, is more than 10 VPBs per hour on Holter ECG. Suppression of ectopic activity of this kind, however, may be clinically unhelpful, as the CAST has shown. Furthermore, among the drugs considered are class Ic and la agents, which, as monotherapy could well be more pro-arrhythmic than antiarrhythmic in certain categories of patients. Most of the time both tests are required to obtain optimal information on the response to therapy. Despite the lack of hard data, electrophysiologyguided drug selection is important in eliminating empiricism in clinical practice and its value for risk stratification is well proven. Thus, the demonstration of inducible arrhythmias in cases treated with drugs should alert the physician about the possibility of an adverse prognosis, and alternative modes of therapy, such as the implantable defibrillator, should be considered. There are certain occasions when PES is of limited value as a treatment selection guide. In sudden cardiac death survivors with severely compromised LV function (EF
How to prescribe and manage antiarrhythmic drug therapy A. J. CAMM AND D. KATRITSIS
Department of Cardiological Sciences, St George's Hospital Medical School, London, U.K.
Summary
The pharmacological approach is the comer-stone of therapy for arrhythmia because it is non-invasive, convenient and widely available. However, the indications for antiarrhythmic therapy in general, as well as the indications for drug therapy as opposed to non-pharmacological therapeutic methods, are far from clearly defined. Among the existing antiarrhythmic drugs, clear reduction of mortality due to arrhythmia has been shown definitively only with beta-blocking agents and possibly with amiodarone. PREDICTION OF EFFICACY
Selection of the appropriate antiarrhythmic drug for management of supra ventricular arrhythmia is potentially rational since it can, in part, be predicted from our knowledge of the mechanism of the arrhythmia and the tissuespecificity of the drugs. Thus, agents prolonging the refractoriness of the atrio-ventricular (AV) node are selected for the treatment of reentrant arrhythmias involving the node, whereas atrio-ventricular reentrant arrhythmias involving accessory pathways can be managed with drugs which affect other parts of the macrocircuit which supports the arrhythmia. Ventricular tachyarrhythmias are difficult to treat and the drug selection is more empirical. Drugs such as amiodarone or sotalol are the first choice agents for this purpose. Specific drug therapy can be guided by invasive electrophysiology studies, Holter monitoring and exercise testing. In centres with electrophysiology facilities, programmed electrical stimulation is currently used for risk stratification of arrhythmia patients and for guidance of drug selection and treatment efficacy in patients with monomorphic ventricular tachycardia and in survivors of ventricular fibrillation (VF) with preserved left ventricular (LV) function (ejection fraction (EF) >30%). Although limited data from one randomized study have suggested that programmed electrical stimulation is superior to non-invasive methods, such as electrocardiographic monitoring, for predicting treatment efficacy, this issue is currently under further investigation. Furthermore, the time limitations of these predictions, i.e. the history of arrhythmias treated by drugs selected by the invasive or the non-invasive approach, is entirely unknown. Signal averaged electrocardiography for detection of late potentials and assessment of cardiac autonomic tone by means of heart rate variability analysis are also being evaluated. It has been suggested that drug level Conespondcnct: Profeisor A. John Camm, Department of Cardiological Sciences, St George's Hospital Medical School, London, U.K 0195-668X/92/OF0044 + 09 S08.00/0
measurement may be essential formonitoring antiarrhythmic therapy. Alternatively, ensuring that the electrocardiographic response to antiarrhythmic drug therapy is present may be a better approach. SAFETY MONITORING
One of the major problems of almost all antiarrhythmic drugs is the narrow therapeutic-toxic margin they display in clinical practice. The most important, life-threatening side effect of antiarrhythmic drugs is pro-arrhythmia, which gives rise to considerable concern about their clinical use. It is not possible to eliminate the risk of proarrhythmia, but patient monitoring with electrolyte measurement, drug level assays, Holter recordings, exercise testing and electrophysiological reassessment may reduce this possibility. The immediate aim of antiarrhythmic therapy is to suppress the arrhythmia, but its overall beneficial effect can only be confirmed by demonstration of a reduction in the morbidity and mortality associated with the arrhythmia under treatment. The institution of antiarrhythmic therapy should be initiated in seriously symptomatic or life-threatening arrhythmias after careful consideration of the benefit-risk ratio. Introduction
During the last decade, exciting progress has been made in the treatment of arrhythmias, not only by development of new drugs, but also by the introduction of alternative methods of treatment, such as implantable devices, and catheter or surgical ablation1'"41. The pharmacological approach remains the corner-stone of therapy. It may not be always the cheapest or the most efficient mode of treatment15' but it is non-invasive, more convenient and widely available. However, despite the long use of numerous antiarrhythmic agents, some questions still remain without a definitive answer: what are the specific indications for these drugs, on what grounds should they be selected for each case and how should the patient be monitored during such treatment? Indications for therapy
The indications for antiarrhythmic therapy, in general, are far from clearly defined, but most authorities would agree that symptomatic or life-threatening arrhythmias deserve specific treatment'2"41. The advent of catheter and surgical ablation techniques for a curative treatment of arrhythmias has made this modality, whenever feasible, the treatment of choice for the management of such > 1992 The European Society of Cardiology
•s-
Managing antiarrhythmic drug therapy 45
patients. When radical treatment is not possible or is accompanied by a high operative risk, such arrhythmias should be treated with drugs, implantable devices or both. However, whether such therapy improves mortality and reduces the incidence of cardiac sudden death and how drug therapy, in particular, compares with alternative therapies is not yet known. In addition, the choice of the initial agent for a particular arrhythmia remains largely empiric. Choice of agent—prediction of efficacy SUPRAVENTRICULAR AND ATRIOVENTRICULAR (USING ACCESSORY PATHWAYS) ARRHYTHMIAS
Selection of the appropriate drug for supraventricular arrhythmias may be quite logical since efficacy can be predicted from a knowledge of the mechanism of the arrhythmia and the tissue-specificity of the drugs. Thus, agents prolonging the refractoriness of the AV node (calcium antagonists, beta-blockers and digoxin) are selected for the treatment of reentrant arrhythmias involving the node, whereas atrioventricular reentrant arrhythmias involving accessory pathways can be interrupted either at the node or the pathway (classes la, Ic and III)141. In chronic atrial fibrillation, therapy is usually aimed at the control of the ventricular response with AV nodal blocking agents, whereas for paroxysmal atrial fibrillation (AF) drugs stabilizing the atrium (such as class la, Ic and III) are used'61. For paroxysmal atrial flutter, no entirely satisfactory drug exists but in our experience sotalol[7] is a useful agent for this purpose. In the absence of ventricular disease, the risk of therapy with class Ic agents may be considerably less than found in the CAST population181. However, reservations have been recently expressed about the safety of flecainide as well as quinidine in the setting of atrial fibrillation, and the matter probably needs further consideration and study. The administration of flecainide in patients with chronic or paroxysmal atrial fibrillation has been found to be complicated by life-threatening ventricular arrhythmias'9"121 and this pro-arrhythmic effect might be associated with exercise1"1. Falk'"1 reported on three such patients receiving flecainide for chronic or paroxysmal atrial fibrillation. Two of them developed ventricular arrhythmias during peak exercise without any previous symptoms or evidence from Holter monitoring of sustained ventricular tachycardia. A meta-analysis of clinical studies comparing quinidine with placebo for long-term prevention of atrial fibrillation after cardioversion from this arrhythmia showed an increased mortality in patients who were treated with the drug*131. Although this report has included only part of the available data on the subject, it questions the role of quinidine in the long-term treatment of this patient group. These reports indicate the need for a more thorough assessment of the safety profile of class I drugs. Supraventricular arrhythmias generally have a good prognosis, especially when associated with structurally normal hearts, but they may all result in sudden cardiac death'14151 and some form of treatment may be necessary not only for the highly symptomatic cases. The efficacy of
the proposed drugs can be assessed in the electrophysiology laboratory by demonstrating lack of inducibility of the reentrant arrhythmia and, in the case of atrioventricular reentrant arrhythmias, by additional measurement of the achieved prolongation of refractoriness of the accessory pathway1'5'161. This usually requires invasive electrophysiology studies: alternatively, transoesophageal pacing can be used, but this technique may at times be more uncomfortable for the patient than the insertion of intracardiac electrodes. In atrial fibrillation, electrocardiographic monitoring and symptomatic improvement are the only guides for assessing treatment efficacy. Although ECG monitoring and exercise testing can be used for the long-term follow-up of these patients'41, no data exist to validate the clinical benefits of this practice. Unfortunately, the long-term management and follow-up of these patients is based on empiricism and the clinician's judgement for every individual case. VENTRICULAR TACHYARRHYTHMIAS
The proper management of ventricular arrhythmias represents a serious challenge for the clinical cardiologist and the available data do not allow answers to several important questions. Sudden cardiac death, which is probably caused by ventricular arrhythmias in the majority of cases'17'181, remains a major health problem despite the widespread use of antiarrhythmic drugs. The patient with compromised LV function and sustained ventricular tachycardia or VF has a sudden death rate of approximately 20 to 30% per year if treated empirically"9"231. With the use of electrophysiology- or ECG monitoringguided drug therapy and possibly amiodarone (as well as implantable defibrillators) the sudden death rate may be reduced to 5-10% per year123"271. Thus, we can project that careful therapeutic intervention with drugs may reduce the incidence of sudden death in patients with malignant arrhythmias, but definitive evidence based on controlled trials is missing. As yet, with the exception of beta-blockers in post-infarct patients'281 (and, perhaps, amiodarone in hypertrophic cardiomyopathy'291 and post-infarct patients'301), no convincing evidence has been presented that suppression of spontaneously occurring arrhythmias by antiarrhythmic drugs decreases the incidence of arrhythmic death. Furthermore, in the case of nonsustained ventricular tachycardia (VT) or asymptomatic ventricular ectopic activity in the post-infarction patient, there is enormous controversy regarding the correct management'311. Ventricular tachyarrhythmias are more difficult to treat compared with supraventricular arrhythmias. When drug therapy is chosen, the physician has two options: empirical or guided therapy. For the empirical option, drugs such as amiodarone or sotalol appear to be the first choice'32"341, having demonstrated maximum efficacy in the comparative published series. Specific drug therapy can be guided by invasive studies, such as programmed electrical stimulation, or non-invasive ones, such as Holter monitoring and exercise testing. The non-invasive approach begins with determination of the frequency and complexity of the ventricular
46 A.J. Camm andD. Katritsis
arrhythmia in a drug-free state by means of ambulatory electrocardiographic monitoring and exercise testing. Successful therapy is then defined by suppression of this spontaneous arrhythmia'24'35-'61. Graboys et a/.'241 studied 123 cardiac arrest survivors by means of 48-h Holter monitoring (100 patients) and exercise testing (60 patients). Suppression of non-sustained runs of VT or R-on-T ventricular premature beats (VPBs) identified on Holter monitoring or during exercise testing, was accompanied by reduced mortality (annual incidence of sudden death 2-3% in patients with effective therapy vs 43-6% in patients with ineffective therapy). This study suffered from several methodological problems, the most important of which is the adoption of the so-called 'fail-safe' programme of drug protection, i.e. the administration of an additional antiarrhythmic drug to the identified effective agent. The invasive approach employs programmed electrical stimulation (PES) in a drug-free state that induces the patient's ventricular arrhythmia. Successful therapy is then defined by suppression of the inducibility of the tachycardia'37"40'. Sustained monomorphic VT can be induced by PES in a large majority of patients who present with this arrhythmia, the rate of inducibility being more than 90% in patients with ischaemic heart disease (IHD) but somewhat lower in patients with cardiomyopathy or normal heart VT14142-31'. In survivors of cardiac arrest, PES results in the induction of sustained ventricular tachycardia, polymorphic VT/VF in up to 80% of patients'4344'. In sudden cardiac death survivors, polymorphic VT/VF are accepted as end-points to guide the selection of antiarrhythmic therapy122'. Although there is a recognised day-to-day variability in the mode of induction, rate and electrocardiographic morphology of induced VT in up to 40% of patients'451, PES allows the selection of a drug that prevents induction of the clinical arrhythmia in approximately 20-50% of patients with ventricular tachyarrhythmias'42'46'481. These patients are at a significantly lower risk for recurrent spontaneous ventricular tachycardia and sudden death than patients in whom a suppressive drug cannot be identified'21 •2Z40'49'. Retrospective analyses'50-511 and concordance studies'5"3' have suggested that the invasive approach predicts the prevention of VT recurrence better than the non-invasive approach. There is also evidence from the one randomized study so far available, that therapy selected by electrophysiological testing can prevent recurrences of VT better than that selected by Holter monitoring and exercise testing (Fig. I)'54'. Significant differences were also observed when amiodarone recipients were excluded. Unfortunately, the number of enrolled patients was rather small (57 patients) for the extraction of defined conclusions. The ESVEM study (Electrophysiologic Study Versus Electrocardiographic Monitoring)'551, a large multicentre trial, addresses the same question (Fig. 2). Preliminary analysis of the results has shown no significant differences between the invasive and non-invasive groups in terms of cardiac death and arrhythmia recurrence over a 4 year follow-up, although at 1 -5 years, there was a trend for less arrhythmia recurrences in the PES group (Fig. 2).
oo Holler PES Two-year follow-up
Figure 1 Recurrences,of tachyarrhythmia and sudden death in patients treated by the invasive and non-invasive approaches in the Calgary study (Mitchell el a/.|M|). 0 = arrhythmia /> = 002; • = sudden death /> = NS.
We believe that the two approaches should be considered complementary rather than competitive. The information derived from them is not comparable: ECG monitoring registers the effect of an intervention on VPBs or a spontaneously occurring arrhythmia, whereas PES induces the clinical arrhythmia and gives information on the effect on its substrate. One of the inclusion criteria for the ESVEM, for example, is more than 10 VPBs per hour on Holter ECG. Suppression of ectopic activity of this kind, however, may be clinically unhelpful, as the CAST has shown. Furthermore, among the drugs considered are class Ic and la agents, which, as monotherapy could well be more pro-arrhythmic than antiarrhythmic in certain categories of patients. Most of the time both tests are required to obtain optimal information on the response to therapy. Despite the lack of hard data, electrophysiologyguided drug selection is important in eliminating empiricism in clinical practice and its value for risk stratification is well proven. Thus, the demonstration of inducible arrhythmias in cases treated with drugs should alert the physician about the possibility of an adverse prognosis, and alternative modes of therapy, such as the implantable defibrillator, should be considered. There are certain occasions when PES is of limited value as a treatment selection guide. In sudden cardiac death survivors with severely compromised LV function (EF
