European Heart Journal (1992) 13 (Supplement F), 53-55
Who should be treated with antiarrhythmic drugs and why? K. ADALET AND R. W. F. CAMPBELL
Academic Cardiology, Freeman Hospital, Newcastle upon Tyne, U.K.*
Introduction
Symptomatic and/or haemodynamically significant arrhythmias
Symptomatic and/or haemodynamically significant arrhythmias demand attention. Affected patients will as a minimum require reassurance; others will need treatment. Any brady- or tachyarrhythmia may cause symptoms or haemodynamic upset but there is great inter-individual variation in the perception of arrhythmias. Some patients are apparently unaware of episodes of relatively rapid ventricular tachycardia while others may complain bitterly of isolated ectopic beats. In general, for tachyarrhythmias, symptoms are related to the rate and duration of the arrhythmia (Fig. 1). Similarly, rate and duration are of relevance in the perception of bradyarrhythmias but here the relationship is particularly variable perhaps because the associated symptoms may be subtle. For instance, lassitude and reduced effort tolerance are insidious features of complete heart block when ventricular rates are in the range 30 to 50 beats per minute. Despite the great variety of arrhythmias which create symptoms or haemodynamic upset, there are some general principles for management. When the arrhythmia is not a direct threat to life, treatment may need not achieve •Department supported by ihe British Heart Foundation. Correspondence: Professor R. W. F. Campbell, Academic Cardiology, Freeman Hospital, Newcastle Upon Tyne, NE7 7ON. 0195-668X/92/0F0053 + 03 $08.00/0
Prognostically significant arrhythmias
Prognostically significant arrhythmas are an important clinical problem and have been the subject of debate and investigation. These arrhythmias do not in themselves cause symptoms but they are associated with an adverse late prognosis. Until relatively recently, it was widely held that patients would benefit from the abolition of these events, but in most situations this has not proved rewarding. High frequency ventricular ectopic beats postmyocardial infarction are associated with a relatively high late mortality111, but their suppression with a variety of antiarrhythmic drugs has proved of no benefit. The early
Arrhythmia duration
Figure 1 The degree of symptoms. Any tachyarrhythmia may cause symptoms of haemodynamic upset. As shown, in general, the degree of symptoms are related to the rate and duration of the arrhythmia. © 1992 The European Society of Cardiology
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on June 7, 2016
The mere presence of an arrhythmia does not necessarily mandate that it be treated. New evidence has forced critical re-evaluation of the risk-benefits of antiarrhythmic intervention and has focused attention on the sometimes poor protection which can be offered by currently available strategies against lethal arrhythmias. These issues have also exposed limitations in knowledge of the natural history of arrhythmias, the arrhythmogenic implications of disease and of the mechanism of action of antiarrhythmic drugs. Disillusionment with antiarrhythmic therapy has prompted some to suggest that almost all arrhythmias be ignored, but patients dictate otherwise. Many arrhythmias cause symptoms, many seriously interfere with the quality of life and some directly threaten life. Five arrhythmia groups can be identified. Each group requires a different management approach. These arrhythmia groups comprise the following: symptomatic and/or haemodynamically significant arrhythmias, prognostically significant arrhythmias, latent arrhythmias, anticipated arrhythmias and benign arrhythmias.
more than symptom control. There is nothing to gain from complete arrhythmia suppression, which is likely to require high drug doses with the attendant risk of toxicity. The choice of treatment will depend upon the nature of the arrhythmia and the severity of the symptoms. Reassurance, drugs, radiofrequency (RF) ablation, devices, and surgery may all have application in this category of arrhythmia. Arrhythmias with major haemodynamic effects will need more aggressive management but prevention of haemodynamic upset may reasonably be accepted as an end-point for therapy. This may be achieved in some patients without complete abolition of the arrhythmias as, for instance, the slowing of a tachyarrhythmia or its conversion to a non-sustained form. Very little scientific investigation of such 'partial' treatment end-points has been undertaken, but in clinical practice they appear acceptable for a proportion of patients.
54
K. Adalet and R. W. Campbell
studies of drug therapy for these patients were small and the results were not of statistical significance121. The Cardiac Arrhythmia Suppression Trial (CAST)131 changed the situation by demonstrating the adverse risk-benefit of ventricular ectopic beat suppression by a variety of Vaughan Williams Class I antiarrhythmic drugs. Sadly, this result has been extrapolated to the use of these drugs in other situations without evidence that such is a reasonable inference. Nonetheless, for myocardial infarction patients, it is prudent to consider ventricular ectopic beats as markers of an adverse prognosis but not the mechanism of ultimate demise of the patient. High frequency ventricular ectopic beats post-infarction should prompt a thorough evaluation of cardiovascular risk rather than an automatic prescription of antiarrhythmic therapy. Similarly, ventricular ectopic beats in patients with heart failure141 and aortic stenosis'51 are of prognostic significance but their suppression is not a rewarding clinical approach.
Latent arrhythmias are those for which the electrophysiological substrate exists but which have not yet occurred spontaneously. These arrhythmias can be revealed by the delivery of appropriate triggers, as for instance during programmed electrical stimulation. Patients with evidence of pre-excitation on their surface ECG but who have had no arrhythmia are in this category. There is great debate about the correct management of patients with asymptomatic Wolf-Parkinson-White syndrome (WPW) (strictly, the term WPW applies to the combination of the surface ECG features of pre-excitation and arrhythmias). There is a risk of sudden death in WPW'61 but this complication probably has been overemphasised. Nonetheless, some have advocated that all patients be considered at risk of sudden death unless there is evidence that their pathway is 'safe'. To establish the risk of the pathway, acute drug testing171 and exercise testing have been advanced as non-invasive risk assessment methods, but definite conclusions are established in only a minority of patients and may not be entirely reliable. Even the 'gold standard' of invasive electrophysiological investigation may not assess risk unless catecholamine stress is also employed. When a patient's accessory pathway is defined as high risk, treatment is appropriate, otherwise there would be little justification for having performed the test. In the past, drugs have been the mainstay of treatment. There is growing interest in non-pharmacological treatment, with RF ablation'81 supplanting surgery, since affected patients often are young, will need to take longterm therapy and will be at increasing risk if any doses are missed. There is little to support the treatment of asymptomatic patients whose pathway appears not to pose a risk. If and when these patients develop an arrhythmia, they will not succumb. They can seek medical advice and at that time consider the risk-benefits of treatment. By this strategy, at least some patients may escape taking chronic antiarrhythmic therapy. Invasive electrophysiological testing is the most sensitive and specific mechanism of identifying a second
Anticipated arrhythmias
Anticipated arrhythmias are those which can reasonably be predicted from a knowledge of the patient and the underlying disease. The electrophysiological substrate is not present and thus cannot be exposed by provocative manoeuvres. Arrhythmias in this category include ventricular arrhythmias in the acute phase of myocardial infarction'151, reperfusion arrhythmias'16', recurrences of out-of-hospital cardiac arrest in patients who have not sustained acute myocardial infarction'171, and arrhythmias associated with Prinzmetal's variant angina'181. In each of these cases, the modulation and/or progression of the underlying disease process can be incriminated in the anticipated development of the arrhythmias. Many relate to recurrent ischaemia and therefore modification of the basic disease process may be more appropriate than an antiarrhythmic strategy. Some post-myocardial infarction arrhythmias are also in this category, but at present it is not possible to identify the high risk post-myocardial infarction patient with sufficient precision'"'. Some postmyocardial infarction deaths will be a consequence of a lethal arrhythmia; a proportion will be primary, and some merely secondary to a further ischaemicevent. In addition, post-myocardial infarction death may also occur as a consequence of cardiac rupture or a new fatal infarction. Benign arrhythmias
Benign arrhythmias are those which cause no symptoms, or haemodynamic upset and which are not of prog-
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on June 7, 2016
Latent arrhythmias
category of latent arrhythmias—post myocardial infarction ventricular tachycardia'91. In some patients, the process of infarction creates an electrophysiological substrate for ventricular tachycardia. This remains dormant until appropriate triggers occur. Triggers may arise spontaneously or may be delivered artificially by programmed electrical stimulation'101. There is sufficient evidence to recommend that therapy be prescribed for patients with spontaneous post-myocardial infarction ventricular tachycardia; this is best chosen on the basis of electrophysiological testing. In patients in whom the latent arrhythmia is exposed by electrophysiological testing, the risk of spontaneous events is sufficiently high to seek a suppressive management strategy, although this approach is less well supported by currently available evidence. The optimal strategy for induced non-sustained ventricular tachycardia is still controversial, but such patients do not have a normal prognosis and for them there may be value in offering electrophysiologically guided therapy1"'121. In both these categories of patient, the arrhythmia need specific attention, but the importance of the underlying disease should not be overlooked. Its modification may be a complementary or alternative management strategy1'31. In these patients, signal averaging may be useful to screen for patients at risk, but this technique does not have the sensitivity or specificity of electrophysiological study, and disappointingly, it gives no therapeutic assistance1'41.
Who should be treated with antiarrhythmic drugs? 55
Conclusions
Arrhythmias have never been easy to manage but at present they pose greater therapeutic problems than ever. Antiarrhythmic drugs are powerful but have associated risks. Antiarrhythmic drugs offer a complex spectrum of action even as individual agents but more so in combination. Some antiarrhythmic agents such as amiodarone, propafenone and sotalol have more than one antiarrhythmic action. This, in part, may be responsible for their clinical efficacy and for their wide spectrum of action. Specific arrhythmias, which in one clinical setting have great importance, may be no more than a cosmetic blemish in another situation. Additionally, more is now known about the underlying mechanism of arrhythmias such that for some, a cure is possible, often without recourse to surgery. To assess the importance of an arrhythmia correctly for an individual patient and to select the best therapy is a clinical challenge that cannot be solved by consulting consensus protocols'221. There is still insufficient understanding of arrhythmias and treatment strategies to establish widely acceptable clinical management protocols, but there has been sufficient progress in this field to anticipate that such will happen, at least for common problems, in the near future. References [1] Moss AJ. Clinical significance of ventricular arrhythmias in patients with and without coronary artery disease. Prog Cardiovasc Dis 1980; 23: 33-52.
[2] May GS, Eberlein KA, Furberg CD, Passamani ER, DeMets DL. Secondary prevention after myocardial infarction: A review of long-term trials. Prog Cardiovasc Dis 1982; 24: 331-52. [3] 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 1989; 321:406-11. [4] Cleland JGF, Dargie HJ, Ford I. Mortality in heart failure: Clinical variables of prognostic value. Br Heart J 1987; 58: 572-82. [5] Chizner MA, Pearle DL, de Leon AC. The natural history of aortic stenosis in adults. Am Heart J 1980; 99:419-24. [6] Dreifus LS, Haiat R, Waranabe Y, Arriaga J, Reitman N. Ventricular fibrillation: A possible mechanism of sudden death in patients with Wolff-Parkinson-White syndrome. Circulation 1971; 43: 520-7. [7] Wellens HJJ, Braat S, Brugada P, Gorgels APM, Bar FW. Use of procainamide in patients with the Wolff-Parkinson-White syndrome to disclose a short refractory period of the accessory pathway. Am J Cardiol 1982; 50: 1087-9. [8] Calkins H, Iangberg, J, Sousa J, el al. Radiofrequency catheter ablation of accessory connections in 250 patients: Abbreviated therapeutic approach to Wolff-Parkinson-White syndrome. Circulation 1992; 85: 1337-46. [9] Bhandari A, Rose J, Kotlewski A, Proce S, Rahimtoola SH, Wu D. Frequency and significance of induced sustained ventricular tachycardia or fibrillation 2 weeks after acute myocardial infarction. Am J Cardiol 1985; 56: 737-42. [10] ArnsdorfMF. Intracardiac electrophysiologic studies for drug selection in ventricular tachycardia: The need for new approaches based in perturbations of the electrophysiologic matrix. Circulation 1987; 75(Suppl I): 137-9. [11] Buxton AE, Marchlinski FE, Flores BT, Miller JM, Doherty JM, Josephson ME. Non sustained ventricular tachycardia in patients with coronary artery disease: Role of electrophysiologic study. Circulation 1987; 75: 1178-85. [12] Wilber DJ, Olshansky B, Moran JF, Scanlon PJ. Electrophysiological testing and nonsustained ventricular tachycardia. Use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation 1990; 82: 350-8. [13] Kelly P, Ruskin JN, Vlahakes GJ, Buckley MJ, Freeman CS, Gran H. Surgical coronary revascularization in survivors of prehospital cardiac arrest; its effect on inducible ventricular arrhythmias and long-term survival. J Am Coll Cardiol 1990; 15:267-73. [ 14] Nalos PC, Gang ES, Manell WJ, Ladenheim M L, Lass Y, Peter T. The signal-averaged electrocardiogram as a screening test for inducibility of sustained ventricular tachycardia in high risk patients: A prospective study. J Am Coll Cardiol 1987; 9:539-48. [15] Campbell RWF, Murray A, Julian DG. Ventricular arrhythmias is first 12 hours of acute myocardial infarction. Natural history study. Br Heart J 1981; 46: 351-7. [16] Kersschot IE, Brugada P, Ramentol M, el al. Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: A prospective randomised study. J Am Coll Cardiol 1986; 7: 1234-^*2. [17] Wilber DJ, Garan H, Finkelstein D, el al. Out-of-hospital cardiac arrest. Use of electrophysiologic testing in the prediction of long-term prognosis. N Engl J Med 1988; 318: 19-24. [18] Scrutino D, de Toma L, Mangini SG, et al. Ischaemia related ventricular arrhythmias in patients with variant angina pectoris. Eur Heart J 1984; 5: 1013-22. [19] Ruskin JN. Role of invasive electrophysiological testing in the evaluation and treatment of patients at high risk for sudden cardiac death. Circulation 1992; 85{Suppl I): I-152-1-159. [20] Kennedy HL, Pescarmona JE, Bouchard RJ, Goldberg RJ. Coronary artery status of apparently healthy subjects with frequent and complex ventricular ectopy. Ann Intern Med 1980; 92: 179-85. [21] Campbell RWF. Ventricular arrhythmias in normal individuals and athletes. Eur Heart J 1988; 9: 113-7. [22] Campbell RWF. Assessment of the risk benefit ratio for antiarrhythmic drug use. Drugs 1988; 36: 616-32.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on June 7, 2016
nostic significance. If they can be positively identified they should not be treated. Treatment would offer the patient nothing other than the risks of unwanted effects. Supraventricular and ventricular ectopic beats in normal individuals fall within this category, but there are two caveats. The definition of 'normality' based on history and examination alone is not reliable. An ECG and an echocardiogram will expose cardiovascular abnormality in some apparently normal individuals. This information would change the implication of the arrhythmia from one which could be benign to one which may have important prognostic implications. There is no easy or logical stoppoint for investigations. Coronary angiography has, for instance, revealed occult but significant coronary artery disease in over 20% of apparently normal and symptomless subjects with ventricular ectopic beats'201. AV conduction disturbances are remarkably common in normal subjects, as has been revealed by 24 h ambulatory monitoring1211. Even transient periods of second-degree heart block may occur, probably related to high vagal tone. Much remains to be learned of the range of normality associated with high vagal tone, particularly in the setting of well trained individuals. Unless associated with symptoms, these rhythm disturbances should be considered benign. More controversially, the accelerated idio-ventricular rhythm which commonly accompanies successful thrombolytic therapy can be considered benign. It rarely causes symptoms, it is not usually of haemodynamic significance and, representing as it does reperfusion, it may betoken a good rather than a bad prognosis. It does not require treatment.
Who should be treated with antiarrhythmic drugs and why? K. ADALET AND R. W. F. CAMPBELL
Academic Cardiology, Freeman Hospital, Newcastle upon Tyne, U.K.*
Introduction
Symptomatic and/or haemodynamically significant arrhythmias
Symptomatic and/or haemodynamically significant arrhythmias demand attention. Affected patients will as a minimum require reassurance; others will need treatment. Any brady- or tachyarrhythmia may cause symptoms or haemodynamic upset but there is great inter-individual variation in the perception of arrhythmias. Some patients are apparently unaware of episodes of relatively rapid ventricular tachycardia while others may complain bitterly of isolated ectopic beats. In general, for tachyarrhythmias, symptoms are related to the rate and duration of the arrhythmia (Fig. 1). Similarly, rate and duration are of relevance in the perception of bradyarrhythmias but here the relationship is particularly variable perhaps because the associated symptoms may be subtle. For instance, lassitude and reduced effort tolerance are insidious features of complete heart block when ventricular rates are in the range 30 to 50 beats per minute. Despite the great variety of arrhythmias which create symptoms or haemodynamic upset, there are some general principles for management. When the arrhythmia is not a direct threat to life, treatment may need not achieve •Department supported by ihe British Heart Foundation. Correspondence: Professor R. W. F. Campbell, Academic Cardiology, Freeman Hospital, Newcastle Upon Tyne, NE7 7ON. 0195-668X/92/0F0053 + 03 $08.00/0
Prognostically significant arrhythmias
Prognostically significant arrhythmas are an important clinical problem and have been the subject of debate and investigation. These arrhythmias do not in themselves cause symptoms but they are associated with an adverse late prognosis. Until relatively recently, it was widely held that patients would benefit from the abolition of these events, but in most situations this has not proved rewarding. High frequency ventricular ectopic beats postmyocardial infarction are associated with a relatively high late mortality111, but their suppression with a variety of antiarrhythmic drugs has proved of no benefit. The early
Arrhythmia duration
Figure 1 The degree of symptoms. Any tachyarrhythmia may cause symptoms of haemodynamic upset. As shown, in general, the degree of symptoms are related to the rate and duration of the arrhythmia. © 1992 The European Society of Cardiology
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on June 7, 2016
The mere presence of an arrhythmia does not necessarily mandate that it be treated. New evidence has forced critical re-evaluation of the risk-benefits of antiarrhythmic intervention and has focused attention on the sometimes poor protection which can be offered by currently available strategies against lethal arrhythmias. These issues have also exposed limitations in knowledge of the natural history of arrhythmias, the arrhythmogenic implications of disease and of the mechanism of action of antiarrhythmic drugs. Disillusionment with antiarrhythmic therapy has prompted some to suggest that almost all arrhythmias be ignored, but patients dictate otherwise. Many arrhythmias cause symptoms, many seriously interfere with the quality of life and some directly threaten life. Five arrhythmia groups can be identified. Each group requires a different management approach. These arrhythmia groups comprise the following: symptomatic and/or haemodynamically significant arrhythmias, prognostically significant arrhythmias, latent arrhythmias, anticipated arrhythmias and benign arrhythmias.
more than symptom control. There is nothing to gain from complete arrhythmia suppression, which is likely to require high drug doses with the attendant risk of toxicity. The choice of treatment will depend upon the nature of the arrhythmia and the severity of the symptoms. Reassurance, drugs, radiofrequency (RF) ablation, devices, and surgery may all have application in this category of arrhythmia. Arrhythmias with major haemodynamic effects will need more aggressive management but prevention of haemodynamic upset may reasonably be accepted as an end-point for therapy. This may be achieved in some patients without complete abolition of the arrhythmias as, for instance, the slowing of a tachyarrhythmia or its conversion to a non-sustained form. Very little scientific investigation of such 'partial' treatment end-points has been undertaken, but in clinical practice they appear acceptable for a proportion of patients.
54
K. Adalet and R. W. Campbell
studies of drug therapy for these patients were small and the results were not of statistical significance121. The Cardiac Arrhythmia Suppression Trial (CAST)131 changed the situation by demonstrating the adverse risk-benefit of ventricular ectopic beat suppression by a variety of Vaughan Williams Class I antiarrhythmic drugs. Sadly, this result has been extrapolated to the use of these drugs in other situations without evidence that such is a reasonable inference. Nonetheless, for myocardial infarction patients, it is prudent to consider ventricular ectopic beats as markers of an adverse prognosis but not the mechanism of ultimate demise of the patient. High frequency ventricular ectopic beats post-infarction should prompt a thorough evaluation of cardiovascular risk rather than an automatic prescription of antiarrhythmic therapy. Similarly, ventricular ectopic beats in patients with heart failure141 and aortic stenosis'51 are of prognostic significance but their suppression is not a rewarding clinical approach.
Latent arrhythmias are those for which the electrophysiological substrate exists but which have not yet occurred spontaneously. These arrhythmias can be revealed by the delivery of appropriate triggers, as for instance during programmed electrical stimulation. Patients with evidence of pre-excitation on their surface ECG but who have had no arrhythmia are in this category. There is great debate about the correct management of patients with asymptomatic Wolf-Parkinson-White syndrome (WPW) (strictly, the term WPW applies to the combination of the surface ECG features of pre-excitation and arrhythmias). There is a risk of sudden death in WPW'61 but this complication probably has been overemphasised. Nonetheless, some have advocated that all patients be considered at risk of sudden death unless there is evidence that their pathway is 'safe'. To establish the risk of the pathway, acute drug testing171 and exercise testing have been advanced as non-invasive risk assessment methods, but definite conclusions are established in only a minority of patients and may not be entirely reliable. Even the 'gold standard' of invasive electrophysiological investigation may not assess risk unless catecholamine stress is also employed. When a patient's accessory pathway is defined as high risk, treatment is appropriate, otherwise there would be little justification for having performed the test. In the past, drugs have been the mainstay of treatment. There is growing interest in non-pharmacological treatment, with RF ablation'81 supplanting surgery, since affected patients often are young, will need to take longterm therapy and will be at increasing risk if any doses are missed. There is little to support the treatment of asymptomatic patients whose pathway appears not to pose a risk. If and when these patients develop an arrhythmia, they will not succumb. They can seek medical advice and at that time consider the risk-benefits of treatment. By this strategy, at least some patients may escape taking chronic antiarrhythmic therapy. Invasive electrophysiological testing is the most sensitive and specific mechanism of identifying a second
Anticipated arrhythmias
Anticipated arrhythmias are those which can reasonably be predicted from a knowledge of the patient and the underlying disease. The electrophysiological substrate is not present and thus cannot be exposed by provocative manoeuvres. Arrhythmias in this category include ventricular arrhythmias in the acute phase of myocardial infarction'151, reperfusion arrhythmias'16', recurrences of out-of-hospital cardiac arrest in patients who have not sustained acute myocardial infarction'171, and arrhythmias associated with Prinzmetal's variant angina'181. In each of these cases, the modulation and/or progression of the underlying disease process can be incriminated in the anticipated development of the arrhythmias. Many relate to recurrent ischaemia and therefore modification of the basic disease process may be more appropriate than an antiarrhythmic strategy. Some post-myocardial infarction arrhythmias are also in this category, but at present it is not possible to identify the high risk post-myocardial infarction patient with sufficient precision'"'. Some postmyocardial infarction deaths will be a consequence of a lethal arrhythmia; a proportion will be primary, and some merely secondary to a further ischaemicevent. In addition, post-myocardial infarction death may also occur as a consequence of cardiac rupture or a new fatal infarction. Benign arrhythmias
Benign arrhythmias are those which cause no symptoms, or haemodynamic upset and which are not of prog-
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on June 7, 2016
Latent arrhythmias
category of latent arrhythmias—post myocardial infarction ventricular tachycardia'91. In some patients, the process of infarction creates an electrophysiological substrate for ventricular tachycardia. This remains dormant until appropriate triggers occur. Triggers may arise spontaneously or may be delivered artificially by programmed electrical stimulation'101. There is sufficient evidence to recommend that therapy be prescribed for patients with spontaneous post-myocardial infarction ventricular tachycardia; this is best chosen on the basis of electrophysiological testing. In patients in whom the latent arrhythmia is exposed by electrophysiological testing, the risk of spontaneous events is sufficiently high to seek a suppressive management strategy, although this approach is less well supported by currently available evidence. The optimal strategy for induced non-sustained ventricular tachycardia is still controversial, but such patients do not have a normal prognosis and for them there may be value in offering electrophysiologically guided therapy1"'121. In both these categories of patient, the arrhythmia need specific attention, but the importance of the underlying disease should not be overlooked. Its modification may be a complementary or alternative management strategy1'31. In these patients, signal averaging may be useful to screen for patients at risk, but this technique does not have the sensitivity or specificity of electrophysiological study, and disappointingly, it gives no therapeutic assistance1'41.
Who should be treated with antiarrhythmic drugs? 55
Conclusions
Arrhythmias have never been easy to manage but at present they pose greater therapeutic problems than ever. Antiarrhythmic drugs are powerful but have associated risks. Antiarrhythmic drugs offer a complex spectrum of action even as individual agents but more so in combination. Some antiarrhythmic agents such as amiodarone, propafenone and sotalol have more than one antiarrhythmic action. This, in part, may be responsible for their clinical efficacy and for their wide spectrum of action. Specific arrhythmias, which in one clinical setting have great importance, may be no more than a cosmetic blemish in another situation. Additionally, more is now known about the underlying mechanism of arrhythmias such that for some, a cure is possible, often without recourse to surgery. To assess the importance of an arrhythmia correctly for an individual patient and to select the best therapy is a clinical challenge that cannot be solved by consulting consensus protocols'221. There is still insufficient understanding of arrhythmias and treatment strategies to establish widely acceptable clinical management protocols, but there has been sufficient progress in this field to anticipate that such will happen, at least for common problems, in the near future. References [1] Moss AJ. Clinical significance of ventricular arrhythmias in patients with and without coronary artery disease. Prog Cardiovasc Dis 1980; 23: 33-52.
[2] May GS, Eberlein KA, Furberg CD, Passamani ER, DeMets DL. Secondary prevention after myocardial infarction: A review of long-term trials. Prog Cardiovasc Dis 1982; 24: 331-52. [3] 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 1989; 321:406-11. [4] Cleland JGF, Dargie HJ, Ford I. Mortality in heart failure: Clinical variables of prognostic value. Br Heart J 1987; 58: 572-82. [5] Chizner MA, Pearle DL, de Leon AC. The natural history of aortic stenosis in adults. Am Heart J 1980; 99:419-24. [6] Dreifus LS, Haiat R, Waranabe Y, Arriaga J, Reitman N. Ventricular fibrillation: A possible mechanism of sudden death in patients with Wolff-Parkinson-White syndrome. Circulation 1971; 43: 520-7. [7] Wellens HJJ, Braat S, Brugada P, Gorgels APM, Bar FW. Use of procainamide in patients with the Wolff-Parkinson-White syndrome to disclose a short refractory period of the accessory pathway. Am J Cardiol 1982; 50: 1087-9. [8] Calkins H, Iangberg, J, Sousa J, el al. Radiofrequency catheter ablation of accessory connections in 250 patients: Abbreviated therapeutic approach to Wolff-Parkinson-White syndrome. Circulation 1992; 85: 1337-46. [9] Bhandari A, Rose J, Kotlewski A, Proce S, Rahimtoola SH, Wu D. Frequency and significance of induced sustained ventricular tachycardia or fibrillation 2 weeks after acute myocardial infarction. Am J Cardiol 1985; 56: 737-42. [10] ArnsdorfMF. Intracardiac electrophysiologic studies for drug selection in ventricular tachycardia: The need for new approaches based in perturbations of the electrophysiologic matrix. Circulation 1987; 75(Suppl I): 137-9. [11] Buxton AE, Marchlinski FE, Flores BT, Miller JM, Doherty JM, Josephson ME. Non sustained ventricular tachycardia in patients with coronary artery disease: Role of electrophysiologic study. Circulation 1987; 75: 1178-85. [12] Wilber DJ, Olshansky B, Moran JF, Scanlon PJ. Electrophysiological testing and nonsustained ventricular tachycardia. Use and limitations in patients with coronary artery disease and impaired ventricular function. Circulation 1990; 82: 350-8. [13] Kelly P, Ruskin JN, Vlahakes GJ, Buckley MJ, Freeman CS, Gran H. Surgical coronary revascularization in survivors of prehospital cardiac arrest; its effect on inducible ventricular arrhythmias and long-term survival. J Am Coll Cardiol 1990; 15:267-73. [ 14] Nalos PC, Gang ES, Manell WJ, Ladenheim M L, Lass Y, Peter T. The signal-averaged electrocardiogram as a screening test for inducibility of sustained ventricular tachycardia in high risk patients: A prospective study. J Am Coll Cardiol 1987; 9:539-48. [15] Campbell RWF, Murray A, Julian DG. Ventricular arrhythmias is first 12 hours of acute myocardial infarction. Natural history study. Br Heart J 1981; 46: 351-7. [16] Kersschot IE, Brugada P, Ramentol M, el al. Effects of early reperfusion in acute myocardial infarction on arrhythmias induced by programmed stimulation: A prospective randomised study. J Am Coll Cardiol 1986; 7: 1234-^*2. [17] Wilber DJ, Garan H, Finkelstein D, el al. Out-of-hospital cardiac arrest. Use of electrophysiologic testing in the prediction of long-term prognosis. N Engl J Med 1988; 318: 19-24. [18] Scrutino D, de Toma L, Mangini SG, et al. Ischaemia related ventricular arrhythmias in patients with variant angina pectoris. Eur Heart J 1984; 5: 1013-22. [19] Ruskin JN. Role of invasive electrophysiological testing in the evaluation and treatment of patients at high risk for sudden cardiac death. Circulation 1992; 85{Suppl I): I-152-1-159. [20] Kennedy HL, Pescarmona JE, Bouchard RJ, Goldberg RJ. Coronary artery status of apparently healthy subjects with frequent and complex ventricular ectopy. Ann Intern Med 1980; 92: 179-85. [21] Campbell RWF. Ventricular arrhythmias in normal individuals and athletes. Eur Heart J 1988; 9: 113-7. [22] Campbell RWF. Assessment of the risk benefit ratio for antiarrhythmic drug use. Drugs 1988; 36: 616-32.
Downloaded from http://eurheartj.oxfordjournals.org/ by guest on June 7, 2016
nostic significance. If they can be positively identified they should not be treated. Treatment would offer the patient nothing other than the risks of unwanted effects. Supraventricular and ventricular ectopic beats in normal individuals fall within this category, but there are two caveats. The definition of 'normality' based on history and examination alone is not reliable. An ECG and an echocardiogram will expose cardiovascular abnormality in some apparently normal individuals. This information would change the implication of the arrhythmia from one which could be benign to one which may have important prognostic implications. There is no easy or logical stoppoint for investigations. Coronary angiography has, for instance, revealed occult but significant coronary artery disease in over 20% of apparently normal and symptomless subjects with ventricular ectopic beats'201. AV conduction disturbances are remarkably common in normal subjects, as has been revealed by 24 h ambulatory monitoring1211. Even transient periods of second-degree heart block may occur, probably related to high vagal tone. Much remains to be learned of the range of normality associated with high vagal tone, particularly in the setting of well trained individuals. Unless associated with symptoms, these rhythm disturbances should be considered benign. More controversially, the accelerated idio-ventricular rhythm which commonly accompanies successful thrombolytic therapy can be considered benign. It rarely causes symptoms, it is not usually of haemodynamic significance and, representing as it does reperfusion, it may betoken a good rather than a bad prognosis. It does not require treatment.
