Annotations
failed to show some response, and complete success was seen in 72 per cent. Used intravenously, it was frequently effective when lidocaine had failed, although a relatively high incidence of toxic effects was seen. Nausea or vomiting, particularly after initial bolus injection, occurred in 20 per cent of patients. More worrying, cardiovascular toxicity (hypotension sometimes associated with bradycardia or supraventricular arrhythmias) was observed in 14 per cent of the patients, although most of these were particularly ill with acute myocardial infarction and had received many other anti-arrhythmic drugs. Its present status as an intravenous agent, therefore, is probably as additional or alternative therapy in cases otherwise uncontrolled. Oral Mexiletine has given more encouraging results and is effective, easy to administer, and relatively free from toxic effects. In Edinburgh, a series of 25 patients with chronic ventricular arrhythmias has now undergone long-term therapy for up to eighteen months. Suppression of ventricular arrhythmias was checked at frequent outpatient visits and by portable 24-hour electrocardiogram tape recordings. In addition, efficiency of treatment was assessed by observing the effect of withdrawal of therapy in hospitalized patients with continuous monitoring of the electrocardiogram (Fig. 1). These studies were uncontrolled, but the effectiveness and absence of clinical, hematologic, or biochemical evidence of toxicity are very encouraging. Furthermore, therapeutic plasma concentrations are easily maintained with an eighthour oral dose regimen. Currently, the drug is being further assessed by long-term controlled studies. Although relatively early, it appears that Mexiletine is potentially useful-particularly as a long-term oral antiarrhythmic-and, as such, deserves further evaluation.
R. G. Talbot, M.R.C.P., M.R.A.C.P. Department of Cardiology The Rqal Infirmary Edinburgh, EH3, 9YW, Scotland
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15. REFERENCES 1.
2.
3.
Lown, B., Temte, J. V., and Arter, W. J.: Ventricular tachyarrhythmias, clinical aspects, Circulation 47: 1364, 1973. Jewitt, D. E.: Treatment of ventricular arrhythmias associated with myocardial infarction. In: Proceedings of United Kingdom -Scandinavian Cardiology Conference, Kennedy, J. L., editor, 1972. Kotler, M. N.: Ventricular extrasystoles. Prognostic sig-
Tachyarrhythmias attacks
and transient
cerebral
It has been extensively documented in the literature that extreme bradycardia and cardiac standstill are commonly associated with signs of generalized cerebral ischemia. Several authors also mention that paroxysmal tachyarrhythmias may induce dizziness or syncope, but only very few studies
538
16.
17.
nificance with respect to sudden death in late postmyocardial infarction patients, Circulation 47:959, 1973. Chiang, B. N., Perlmam, L. V., Ostrander, L. D., et al.: Relationship of premature systoles to coronary heart disease and sudden death in the Tecumseh epidemiologic study, Ann Intern. Med. 70:1159, 1969. Kannel, W. B., Dawber, T. R., and McNamara, P. M.: Detection of the coronary-prone adult: The Framingham Study, J. Iowa Med. Sot. 56:26, 1966. The Coronary Drug Project Research Group (Blackburn, S., and Tominaga, S., presenters): post-infarction electrocardiographic findings and prognosis, Circulation 44:@uppl. II), 154, 1971. Hinkle, L. E., Carver, S. T., and Stevens, M.: The frequency of asymptomatic disturbances of cardiac rhythm and conduction in middle-aged men, Am. J. Cardiol. 24:629, 1969. Taylor, J., Kosowsky, B., and Lown, B.: Complications of procainamide in a prospective antiarrhythmic study, Circulation 44XSuppl. II) 43, 1971. Kosowsky, B. D., Taylor, J., Lown, B., and Ritchie, R. F.: Long-term use of procainamide following acute myocardial infarction, Circulation 47:1204, 1973. Selzer, A., and Wray, H. W.: Quinidine syncope-paroxysmal ventricular fibrillation occurring during treatment of chronic atria1 arrhythmias, Circulation 30:17, 1964. Stone, N., Klein, M. D., and Lown, B.: Diphenylhydantoin in the prevention of recurring ventricular tachycardia, Circulation 43:420, 1971. Elliott, W. C., and Stone, J. M.: Beta-adrenergic blocking agents for the treatment of angina pectoris, Progr. Cardiovasc. Dis 12:83, 1969. Fitzgerald, J. D.: Beta-adrenergic blocking drugs: present position and future development, Acta Cardiol. Suppl. 15:199, 1972. Allen, J. D., Kofi-Ekue, J. M., Shanks, R. G., andzaidi, S. A.: The effect on experimental cardiac arrhythmias of a new anticdnvulsant agent, Ko 1173, and its comparison with phenytoin and procainamide, Br. J. Pharmacol. 39:183, 1970. Singh, B. N., and Vaughan-Williams, E. M.: Investigations of the mode of action of a new antidysrhythmic drug, Kii 1173, Br. J. Pharmacol. 44:1, 1972. Talbot, R. G., Clark, R. A., Nimmo, J., Neilson, J. M. M., Julian, D. G., and Prescott, L. F.: Treatment of ventricular arrhythmias with Mexiletine (K6 1173), Lancet 2:399, 1973. Campbell, N. P. S., Chaturvedi, N. C., Kelly, J. G., Strong, J. E., Shanks, R. G., and Pantridge, J. F.: Mexiletine in the management of ventricular dysrrhythmias, Lancet 2:404, 1973.
ischemic
have provided objective data to assess the real importance of this problem. l-6 The main reason for this lack of data is that intermittent tachyarrhythmias constitute a real diagnostic challenge.‘p3 The routine electrocardiogram is of little help since it is seldom recorded during the acute attack and is
April,
1975, Vol. 89, No. 4
Annotations
I . Routine electrocardiogram tients with dizziness or syncope Table
Normal electrocardiogram: Morphologic abnormalities: Myocardial infarction Left ventricular hypertrophy Abnormal repolarixation Dysrhyfhmias: Premature atria1 contractions Premature ventricular contractions Controlled atria1 fibrillation Sinus bradycardia Conduction disturbances: Left bundle branch block Left anterior hemiblock Bilateral bundle branch block Atrioventricular block, first degree Atrioventricular block, second degree Wolff-Parkinson-White syndrome Normally functioning pacemaker:
in 95 pa53
1 able I I . DCG findings in 95 patients with dizziness or syncope* -. 1. II.
6 1 2
4 1 3 2 1 1 13
III.
IV.
often normal in between5 Continuous monitoring is unappropriate in such cases since it requires hospitalization of otherwise healthy subjects in an intensive-care area where they can only be studied in a resting state. With telemetry the heart rhythm can be followed during certain physical activities. Its use for detection of paroxysmal tachyarrhythmias is, however, limited since the receiver has to be in close vicinity to the patient; furthermore, an observer has to continuously watch the tracing displayed on an oscilloscope to detect major changes in heart rhythm. These diagnostic problems and shortcomings are avoided by continuous electrocardiography on a portable tape recorder, performed dur ing normal daily activities until the symptoms occur (dynamic electrocardiography); this system also includes a method of accelerated tape analysis as described by Holter.7 During the past three years, we have used dynamic electrocardiography (DCG) for detection of cardiac dysrhythmias and evaluation of the effectiveness of chronic antidysrhythmic therapy. Close to 5,000 tape recordings have been performed on 587 patients. In 95 cases, DCG was performed because the patients had shown unexplained dizziness (55 patients) or syncope (40 patients). In all patients the clinical neurologic and cardiac examination was normal; the routine electrocardiogram could not provide an explanation for the symptoms in any of the patients (Table I). The age of the patients ranged from 16 to 81 years (mean 57.8 years). The patients were classified into four categories according to the results of the tape analysis (Table ID. In 22 patients (23.1 per cent) no electrocardiographic abnormalities could be detected on repeated DCG recordings (Group I); in 46 patients (48.4 per cent) the findings definitely correlated with the occurrence of dizziness or syncope (Group ID; findings possibly related to the symptoms were identified in 42 patients (Group III) and 17 patients showed abnormalities of the heart rhythm or conduction not related to the symptoms (Group IV). Similar results have been found by Stern and coworkers4 in a series of 44 patients with complaints of transient cerebral ischemic attacks.
American
Heart Journal
No abnormalities defecfed: Findings definitely correlating with symptoms: Paroxysmal atria1 fibrillation Paroxysmal atria1 flutter Paroxysmal atria1 tachycardia Ventricular tachycardia Sinus bradycardia Sino-atria1 block or standstill Atrio-ventricular block, second degree Atrioventricular block, third degree Defective pacemaker Findings possibly related to symptoms: Frequent premature atria1 contractions Frequent premature ventricular contractions Findings not related to symptoms: Sinus tachycardia (2120 bpm) Sinus bradycardia (
failed to show some response, and complete success was seen in 72 per cent. Used intravenously, it was frequently effective when lidocaine had failed, although a relatively high incidence of toxic effects was seen. Nausea or vomiting, particularly after initial bolus injection, occurred in 20 per cent of patients. More worrying, cardiovascular toxicity (hypotension sometimes associated with bradycardia or supraventricular arrhythmias) was observed in 14 per cent of the patients, although most of these were particularly ill with acute myocardial infarction and had received many other anti-arrhythmic drugs. Its present status as an intravenous agent, therefore, is probably as additional or alternative therapy in cases otherwise uncontrolled. Oral Mexiletine has given more encouraging results and is effective, easy to administer, and relatively free from toxic effects. In Edinburgh, a series of 25 patients with chronic ventricular arrhythmias has now undergone long-term therapy for up to eighteen months. Suppression of ventricular arrhythmias was checked at frequent outpatient visits and by portable 24-hour electrocardiogram tape recordings. In addition, efficiency of treatment was assessed by observing the effect of withdrawal of therapy in hospitalized patients with continuous monitoring of the electrocardiogram (Fig. 1). These studies were uncontrolled, but the effectiveness and absence of clinical, hematologic, or biochemical evidence of toxicity are very encouraging. Furthermore, therapeutic plasma concentrations are easily maintained with an eighthour oral dose regimen. Currently, the drug is being further assessed by long-term controlled studies. Although relatively early, it appears that Mexiletine is potentially useful-particularly as a long-term oral antiarrhythmic-and, as such, deserves further evaluation.
R. G. Talbot, M.R.C.P., M.R.A.C.P. Department of Cardiology The Rqal Infirmary Edinburgh, EH3, 9YW, Scotland
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15. REFERENCES 1.
2.
3.
Lown, B., Temte, J. V., and Arter, W. J.: Ventricular tachyarrhythmias, clinical aspects, Circulation 47: 1364, 1973. Jewitt, D. E.: Treatment of ventricular arrhythmias associated with myocardial infarction. In: Proceedings of United Kingdom -Scandinavian Cardiology Conference, Kennedy, J. L., editor, 1972. Kotler, M. N.: Ventricular extrasystoles. Prognostic sig-
Tachyarrhythmias attacks
and transient
cerebral
It has been extensively documented in the literature that extreme bradycardia and cardiac standstill are commonly associated with signs of generalized cerebral ischemia. Several authors also mention that paroxysmal tachyarrhythmias may induce dizziness or syncope, but only very few studies
538
16.
17.
nificance with respect to sudden death in late postmyocardial infarction patients, Circulation 47:959, 1973. Chiang, B. N., Perlmam, L. V., Ostrander, L. D., et al.: Relationship of premature systoles to coronary heart disease and sudden death in the Tecumseh epidemiologic study, Ann Intern. Med. 70:1159, 1969. Kannel, W. B., Dawber, T. R., and McNamara, P. M.: Detection of the coronary-prone adult: The Framingham Study, J. Iowa Med. Sot. 56:26, 1966. The Coronary Drug Project Research Group (Blackburn, S., and Tominaga, S., presenters): post-infarction electrocardiographic findings and prognosis, Circulation 44:@uppl. II), 154, 1971. Hinkle, L. E., Carver, S. T., and Stevens, M.: The frequency of asymptomatic disturbances of cardiac rhythm and conduction in middle-aged men, Am. J. Cardiol. 24:629, 1969. Taylor, J., Kosowsky, B., and Lown, B.: Complications of procainamide in a prospective antiarrhythmic study, Circulation 44XSuppl. II) 43, 1971. Kosowsky, B. D., Taylor, J., Lown, B., and Ritchie, R. F.: Long-term use of procainamide following acute myocardial infarction, Circulation 47:1204, 1973. Selzer, A., and Wray, H. W.: Quinidine syncope-paroxysmal ventricular fibrillation occurring during treatment of chronic atria1 arrhythmias, Circulation 30:17, 1964. Stone, N., Klein, M. D., and Lown, B.: Diphenylhydantoin in the prevention of recurring ventricular tachycardia, Circulation 43:420, 1971. Elliott, W. C., and Stone, J. M.: Beta-adrenergic blocking agents for the treatment of angina pectoris, Progr. Cardiovasc. Dis 12:83, 1969. Fitzgerald, J. D.: Beta-adrenergic blocking drugs: present position and future development, Acta Cardiol. Suppl. 15:199, 1972. Allen, J. D., Kofi-Ekue, J. M., Shanks, R. G., andzaidi, S. A.: The effect on experimental cardiac arrhythmias of a new anticdnvulsant agent, Ko 1173, and its comparison with phenytoin and procainamide, Br. J. Pharmacol. 39:183, 1970. Singh, B. N., and Vaughan-Williams, E. M.: Investigations of the mode of action of a new antidysrhythmic drug, Kii 1173, Br. J. Pharmacol. 44:1, 1972. Talbot, R. G., Clark, R. A., Nimmo, J., Neilson, J. M. M., Julian, D. G., and Prescott, L. F.: Treatment of ventricular arrhythmias with Mexiletine (K6 1173), Lancet 2:399, 1973. Campbell, N. P. S., Chaturvedi, N. C., Kelly, J. G., Strong, J. E., Shanks, R. G., and Pantridge, J. F.: Mexiletine in the management of ventricular dysrrhythmias, Lancet 2:404, 1973.
ischemic
have provided objective data to assess the real importance of this problem. l-6 The main reason for this lack of data is that intermittent tachyarrhythmias constitute a real diagnostic challenge.‘p3 The routine electrocardiogram is of little help since it is seldom recorded during the acute attack and is
April,
1975, Vol. 89, No. 4
Annotations
I . Routine electrocardiogram tients with dizziness or syncope Table
Normal electrocardiogram: Morphologic abnormalities: Myocardial infarction Left ventricular hypertrophy Abnormal repolarixation Dysrhyfhmias: Premature atria1 contractions Premature ventricular contractions Controlled atria1 fibrillation Sinus bradycardia Conduction disturbances: Left bundle branch block Left anterior hemiblock Bilateral bundle branch block Atrioventricular block, first degree Atrioventricular block, second degree Wolff-Parkinson-White syndrome Normally functioning pacemaker:
in 95 pa53
1 able I I . DCG findings in 95 patients with dizziness or syncope* -. 1. II.
6 1 2
4 1 3 2 1 1 13
III.
IV.
often normal in between5 Continuous monitoring is unappropriate in such cases since it requires hospitalization of otherwise healthy subjects in an intensive-care area where they can only be studied in a resting state. With telemetry the heart rhythm can be followed during certain physical activities. Its use for detection of paroxysmal tachyarrhythmias is, however, limited since the receiver has to be in close vicinity to the patient; furthermore, an observer has to continuously watch the tracing displayed on an oscilloscope to detect major changes in heart rhythm. These diagnostic problems and shortcomings are avoided by continuous electrocardiography on a portable tape recorder, performed dur ing normal daily activities until the symptoms occur (dynamic electrocardiography); this system also includes a method of accelerated tape analysis as described by Holter.7 During the past three years, we have used dynamic electrocardiography (DCG) for detection of cardiac dysrhythmias and evaluation of the effectiveness of chronic antidysrhythmic therapy. Close to 5,000 tape recordings have been performed on 587 patients. In 95 cases, DCG was performed because the patients had shown unexplained dizziness (55 patients) or syncope (40 patients). In all patients the clinical neurologic and cardiac examination was normal; the routine electrocardiogram could not provide an explanation for the symptoms in any of the patients (Table I). The age of the patients ranged from 16 to 81 years (mean 57.8 years). The patients were classified into four categories according to the results of the tape analysis (Table ID. In 22 patients (23.1 per cent) no electrocardiographic abnormalities could be detected on repeated DCG recordings (Group I); in 46 patients (48.4 per cent) the findings definitely correlated with the occurrence of dizziness or syncope (Group ID; findings possibly related to the symptoms were identified in 42 patients (Group III) and 17 patients showed abnormalities of the heart rhythm or conduction not related to the symptoms (Group IV). Similar results have been found by Stern and coworkers4 in a series of 44 patients with complaints of transient cerebral ischemic attacks.
American
Heart Journal
No abnormalities defecfed: Findings definitely correlating with symptoms: Paroxysmal atria1 fibrillation Paroxysmal atria1 flutter Paroxysmal atria1 tachycardia Ventricular tachycardia Sinus bradycardia Sino-atria1 block or standstill Atrio-ventricular block, second degree Atrioventricular block, third degree Defective pacemaker Findings possibly related to symptoms: Frequent premature atria1 contractions Frequent premature ventricular contractions Findings not related to symptoms: Sinus tachycardia (2120 bpm) Sinus bradycardia (
