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Delayed repolarization syndrome
Delayed Repolarization Syndrome
PAUL SCHWEITZER, M.D. HERBERT MARK, M.D. New York, New York
From the Cardiology Section, Department of Medicine, Veterans Administration. Hospital, Bronx, New York, and the Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine, New York, New York. Requests for reprints should be addressed to Dr. Paul Schweitzer, Cardiology Section, Veterans Administration Hospital, 130 West Kingsbridge R&d, Bronx, New York 10466. Manuscript accepted January 27, 1963.
The electrocardiograms of 18 patients with atypical ventricular tachycardia manifested as torsade de pointes, ventricular fibrilloflutter, polymorphous ventricular tachycardia, and uniform ventricular tachycardia were analyzed. The patients were divided into two groups: The first group included 10 patients with prolonged 0-T intervals or abnormal U waves (delayed repolarization) and the second group included eight patients with normal ventricular repolarization. All of the electrocardiographic manifestations of atypical ventricular tachycardia were seen In both groups, regardless of the duration of the Q-T interval or the presence of an abnormal U wave. It is suggested that QRS morphology during the tachycardia is not sufficient to distinguish between delayed repolarization and other causes of atypical ventricular tachycardia. Finally, because the electrocardiogram may vary among different patients and from one episode to the next in a single patient due to abnormal repolarizatlon, it is recommended that the term de/ayed repolarizafion syndrome be used to identify the arrhythmia. In 1966, Dessertenne [l] described torsade de pointes, an atypical ventricular tachycardia that was characterized by continuous change in the direction of the ventricular complexes of the electrocardiogram. Because the majority of patients with torsade de pointes described since that report have a long Q-T interval, it was suggested by some investigators [2,3] that this arrhythmia is pathognomic of delayed repolarization [4-61. According to Slama and co-workers [4] and others [5,6], torsade de pointes also occurs in patients with normal Q-T intervals. On the other hand, not all arrhythmias associated with a prolonged Q-T interval fulfill the criteria for torsade de pointes. In some patients, the rhythm disturbance is suggestive of ventricular fibrillation [ 7,8], while others demonstrate a beat-to-beat variation in the morphology of the QRS complexes [9]. The variability of the electrocardiographic features explains why this arrhythmia has also been referred to as transient [7] or paroxysmal ventricular fibrillation [ lo], polymorphous ventricular tachycardia [ 91, or atypical ventricular tachycardia [ 111. Some investigators prefer an etiologic rather than an electrocardiographic diagnosis, e.g., quinidine syncope [ 121. Reynolds and Vander Ark [ 131, emphasizing the underlying electrophysiologic abnormality, recommended the term delayed repolarization syndrome that will be used in this study. In recent years, an increased number of studies dealing with different aspects of torsade de pointes have been reported. Although some of these reports defined the cause, established diagnostic criteria, and suggested an approach to management of torsade de
September1963
The American Journal of Medicine
Volume 75
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DIAGNOSIS OF DELAYED REPOLARIZATION SYNDROME-SCHWEITZER and MARK
TABLE I
Data on Patients with Delayed Repolarization Syndrome Corrected O-T Interval (seconds)
Cause of Delayed Repolarization Syndrome
Patient Number
Age (Yr)
1 2 3 4
20 48 65 56
0.63 0.56 0.62 0.52
No heart disease Hypertension Coronary artery disease Acute myocardial infarction
? Idiopathic Quinidine Quinidine Procainamide
5
48
0.62
Schizophrenia
Chlorpromazine
6
63
0.54
Quinidine
7 8
84 54
0.52
Chronic obstructive lung disease Atrioventricular block Acute myocardial infarction
9
45
0.52
10
56
0.48
Clinical Diagnosis
Coronary artery disease, ventricular aneurysm Chronic obstructive lung disease
APB = atrial premature beats; VPB = ventricular
Bradycardia Acute myocardial infarction Disopyramide, hypokalemia Quinidine, hypokalemia
premature beats; VT = ventricular
pointes, others contributed to the confusion surrounding the syndrome [l-3,5,6,14]. Whether the term torsade de pointes should be reserved solely for arrhythmias with prolonged Q-T intervals or should be also used for patients with normal Q-T intervals [3,5,6] is a question that has remained unsolved. The purpose of this study is to analyze the electrocardiographic manifestation of malignant ventricular arrhythmias in patients with prolonged Q-T intervals and to reassess the usefulness and the limitation of the electrocardiogram in the differentiation of atypical ventricular tachycardia with normal and long Q-T intervals.
Therapy Propranolol Lidocaine Lidocaine Lidocaine, cardioversion, propranolol Lidocaine, cardioversion Bretylium, pacing
APB and VPB Nonsustained VT
Nonsustained VT
Pacing Bretylium Nonsustained VT
Bretylium, potassium Potassium
Atrial tachycardia tachycardia.
PATIENTS AND METHODS We analyzed the clinical and electrocardiographic findings in 18 patients with atypical ventricular tachycardia. In IO patients the arrhythmia was due to delayed repolarization syndrome, while eight patients had normal or nearly normal Q-T intervals. The age of these patients, their clinical diagnoses, the cause of the rhythm disturbances, and treatment are summarized in Tables I and II.
The most important diagnostic feature of delayed repolarization syndrome is a corrected Q-T interval for heart rate in excess of 0.44 seconds [is] or an uncorrected one measuring 0.50 second or more [ 1 l] According to Moss and Schwartz [ 161, another marker of delayed repolarization is
Data on Patients with Normal Ventricular Repolarization
TABLE II
Corrected Q-T Interval lsecondsl
Patient Number
Age fvr)
1
62
0.48
Cardiomyopathy
2
38
0.43
Cardiomyopathy
3 4
54 72
0.43 0.45
Acute myocardial infarction Acute myocardial infarction
5
56
0.42
Coronary artery disease
6
62
0.40
Coronary artery disease
7
57
0.38
7 Syncope
a
73
0.41
Pneumonia, atrial fibrillation
394
Indication for Antiarrhythmic Drugs
September
1993
Clinical Diagnosis
The American
Journal
of Medicine
Tvpe of Ventricular Bachvcardia Polymorphous ventricular tachycardia Polymorphous ventricular tachycardia Torsade de pointes Torsade de pointes, ventricular fibrillo-flutter Torsade de pointes during electrophysiologic study Torsade de pointes during electrophysiologic study Torsade de pointes during electrophysiologic study Torsade de pointes
Volume
75
Theraw Procainamide,
digoxin
Procainamide,
digoxin
Defibrillation (unsuccessful) Defibrillation, lidocaine Procainamide Procainamide No therapy Digoxin
DIAGNOSIS
an abnormal bifid or sinusoidal T wave. The measurement of the Q-T interval and its differentiation from the U wave may be difficult or impossible in the latter instance. One way to distinguish a bifid T wave from a TU wave is to measure the interval between the two peaks [ 171. An interval 0.15 second or less is consistent with a bifid T wave, and one exceeding 0.15 second suggests that the second peak is a U wave. Differentiation between the T and U wave can be achieved by simultaneous recording of an electrocardiogram and phonocardiogram [ 171. The beginning of the U wave coincides with the second heart sound. Phonocardiography, however, is rarely performed in acutely ill patients and this method is probably of limited practical significance. As noted, delayed repolarization may be diagnosed in patients with long Q-T intervals or in those with abnormal U waves. Diagnostic features of an abnormal U wave have not been fully defined. According to Lepeschkin [ 171, the U wave in the standard limb leads is 0.05 mV or less in 95 to 97 percent of normal subjects, while the amplitude of the U wave in the precordial leads has an upper limit of 0.3 mV. The presence of a prominent U wave or alternation of its amplitude are consistent with delayed repolarization syndrome. The electrocardiographic manifestation of delayed repolarization syndrome varies, and may appear as any of the following arrhythmias. 1. Torsade de pointes [ l-3,14,18]. This arrhythmia is characterized by marked changes in the amplitude and the direction of the vector of the ventricular complex, giving the impression that the QRS complex is twisting around an imaginary baseline. The heart rate varies between 150 and 300 beats per minute and the rhythm is irregular. Paroxysms of torsade de pointes are usually initiated by a late occurring ventricular extrasystole or may be preceded by ventricular couplets or triplets. Sometimes it is necessary to record multiple leads to diagnose torsade de pointes, because the more frequent uniform ventricular tachycardia may be simulated if only a single electrocardiographic lead is recorded. 2. Ventricular fibrillo-flutter [8,19]. This arrhythmia consists of runs of ventricular flutter interrupted by fibrillation. 3. Uniform ventricular tachycardia or ventricular flutter. Bizarre ventricular complexes that fuse with the ST-T segment characterize this arrhythmia. The amplitude of the ventricular deflection is uniform, unlike torsade de pointes. However, differentiation between ventricular tachycardia and ventricular flutter may be difficult, and no clear-cut criteria for their separation have been proposed [ 19,201. A more rapid rate and a transient nature are probably more consistent findings in ventricular flutter than in ventricular tachycardia. Ventricular flutter usually progresses rapidly into ventricular fibrillation. 4. Polymorphous or multiform ventricular tachyardia [ 91. In this arrhythmia, the heart rate varies between 150 and 300 beats per minute and the ventricular deflection changes from beat to beat. Identification of these electrocardiographic manifestations of delayed repolarization syndrome may not always be possible because a change from one configuration to another occurs commonly and is probably itself one of the characteristics of delayed repolarization syndrome.
OF DELAYED REPOLARIZATION
SYNDROME-SCHWEITZER
and MARK
Figure 1. Patient 1, Table 1.Rhythm strip of lead II. The first strip shows regular sinus rhythm and notched T wave with a corrected Q-T interval of 0.63 second. In the second strip, the sinus beats are followed by multiform ventricular extrasystoles and tachycardia. The third and fourth strips are continuous, demonstrating multiform ventricular premature beats and a paroxysm of torsade de pointes.
RESULTS
Delayed Repolarization Syndrome. Clinical data, including the cause of delayed repolarization syndrome, and previous treatment in our 10 patients are presented in Table I. The cause of delayed repolarization syndrome could not be determined in only one patient (Patient 1). The syndrome and associated arrhythmias could be attributed to administration of a single medication in five patients (Patients 2 to 6) and to underlying complete atrioventricular block in another (Patient 7). Patient 8 had an acute myocardial infarction. In two patients (Patients 9 and lo), at least two predisposing causes of delayed repolarization syndrome were present. Both patients were taking class I antiarrhythmic drugs and were hypokalemic. The electrocardiographic manifestations of delayed repolarization syndrome differ in individual patients and ’ may also vary from time to time in a single patient (Figures 1 to 4). The diagnostic criteria for torsade de pointes are fulfilled in Figure 1 (Patient l), which shows a self-terminating episode of torsade de pointes and late multiform ventricular extrasystoles. The variability of the electrocardiogram recorded in a patient with complete atrioventricular block and malfunctioning permanent pacemaker is shown in Figure 2. This patient experienced multiple paroxysms of delayed repolarization syndrome; some appeared as typical torsade de pointes (Figure 2A) and others as ventricular flutterfibrillation, requiring defibrillation (Figure 2C and D). The next case demonstrates some of the difficulties encountered in the diagnosis of delayed repolarization syndrome. The electrocardiogram was recorded in a patient with extensive acute anterior myocardial infarction (Patient 4). The patient had been treated with procainamide for nonsustained ventricular tachycardia
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The American Journal of Medicine
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DIAGNOSIS
Figure 2. Patient 7, Table 1.Rhythm strip of lead II. The underlying rhythm is atrial fibrillation, and the baseline is interrupted by ineffective pacemaker spikes. Strip A shows torsade de pointes and multiform ventricular extrasystoles; the latter are also seen in strip B. Strip C starts with well-defined QRS complexes followed by torsade de pointes. Strip D is consistent with ventricular fibrillo-flutter.
Figure 3. Patient 4, Table I. The rhythm strip is from a 24hour ambulatory electrocardiographic recording of lead V, and VI. The corrected O-T interval measures 0.52 second. In strip A (V,), the sinus rhythm is interrupted by ventricular extrasystoles and a paroxysm of ventricular tachycardia. At the beginning of the tachycardia, the main ventricular deflections are negative, then decrease in amplitude after a few beats and become positive. In lead VI, the QRS complexes are uniform and of small amplitude. In both leads of strip 8, there is uniform ventricular tachycardia.
I
I
Patient 5, Table 1.Rhythm strip of a monitor lead. The corrected Q-T interval measures 0.62 second. At the beginning of tha strip, the sinus beats alternate with multiform ventricular extrasystoles, followed by uniform ventricular tachycardia.
Figure 4.
(6 grams given in divided doses over 24 hours). During the administration of the drug, the corrected Q-T interval increased from 0.42 to 0.52 second. Although the ventricular complexes in V5 resembled torsade de pointes, those in lead VI were uniform and of low voltage (Figure 3A). After 30 seconds, this arrhythmia de-
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generated into ventricular fibrillation, requiring defibrillation. Following this episode, the patient was treated with lidocaine, which temporarily controlled the rhythm disturbance. The tachycardia recurred 45 minutes later, but in this episode the QRS deflection was morphologically uniform in both leads (Figure 3B). Alternating paroxysms of multiform and uniform tachycardia were recorded over the succeeding two to three hours, during which time propranolol was also administered. Finally, the arrhythmia became refractory to lidocaine and propranolol and the patient died. It was assumed that the arrhythmia was caused by the underlying disease rather than by procainamide, because oral administration of this drug rarely causes delayed repolarization syndrome [21]. Rapid degeneration of the ventricular tachycardia into ventricular fibrillation also supported this explanation. However, it is also possible that the
Volume 75
DIAONO~IS OF DELAYED REPOLARIZATIONSYNDROME--SCHWEITZER and MARK
patient had delayed repolarization syndrome, caused by acute myocardial infarction [6,22] and procainamide. The electrocardiogram shown in Figure 4 (Patient 5) also demonstrates that delayed repolarization syndrome can rapidly degenerate into ventricular fibrillation. This patient was admitted to the cardiac care unit for observation because an electrocardiogram taken after he had experienced dizziness revealed a prolonged Q-T interval and multiform ventricular premature beats. This patient had been treated with chlorpromazine. Subsequently, a paroxysm of uniform ventricular tachycardia was recorded, which rapidly deteriorated into ventricular fibrillation, which was successfully treated with direct current countershock. The arrhythmia seemed to be uniform, however, because only a single lead was recorded multiform ventricular tachycardia, or torsade de pointes cannot be excluded. Lidocaine was given subsequently, and there were no recurrences of ventricular tachycardia. Atypical Ventricular Tachycardia with Normal Repolarization. The diagnoses, electrocardiographic findings, and the type of treatment given to eight patients without delayed repolarization syndrome in whom the arrhythmia resembled torsade de pointes or another atypical ventricular tachycardia are listed in Table II. These eight patients form a nonhomogeneous group that can be divided into four subgroups. The first subgroup comprises two patients with cardiomyopathy and severe congestive heart failure. When the electrocardiogram of Patient 1 (Figure 5A) was taken, the patient had normal levels of blood electrolytes and was receiving digoxin and furosemide. The corrected Q-T interval measured 0.48 second and short episodes of polymorphous ventricular tachycardia were noted. Despite the fact that this patient had a slightly prolonged Q-T interval, he was given procainamide, which controlled the arrhythmia (Figure 58) and had no further effect on the Q-T interval. Probably the most important findings that help to exclude delayed repolarization syndrome in this type of patient are the subacute or chronic nature of the arrhythmia and the absence of a cause of delayed repolarization syndrome. However, diagnostic difficulties may arise if the patient is treated with antiarrhythmic drugs. There is a greater risk of malignant ventricular arrhythmia developing in patients with impaired left ventricular function during treatment with quinidine [23]. Accordingly, worsening of a ventricular arrhythmia during the administration of quinidine or another antiarrhythmic drug should raise the possibility of delayed repolarization syndrome. In the second subgroup were two patients with coronary artery disease and ventricular fibrillation. The initial phase of ventricular fibrillation resembled torsade de pointes _inboth of these patients.
Figure 5.
Patient 1, Table II. Two rhythm strips (V2 and V,) in a patient with multiform ventricular tachycardia. The corrected Q-T interval measures 0.48 second. In strip A (V,), sinus rhythm at a rate of 115 beats per minute and polymorphous ventricular tachycardia are seen. Strip 6, which was recorklafter the patient was treated with procainami&, shows regular sinus rhythm and a late ventricular extrasysto/e. The corrected Q-T interval remained unchanged.
The electrocardiogram in Figure 6 was recorded in a patient with acute myocardial infarction. This patient had been taking propranolol for angina pectoris (160 mg per 24 hours) but no class I antiarrhythmic drug. Serum potassium level was normal. Sinus bradycardia was present and the corrected Q-T interval measured 0.43 second. The sinus bradycardia was interrupted by an early ventricular premature beat, which initiated a paroxysm of torsade de pointes. After a single sinus beat, the arrhythmia reappeared and rapidly degenerated into ventricular fibrillo-flutter. Repeat defibrillation failed to restore sinus rhythm and the patient died. The initial paroxysm, which terminated spontaneously, fulfills the diagnostic criteria for torsade de pointes. The slow heart rate and the recent myocardial infarction favored this diagnosis. However, the initiation of the ventricular arrhythmia by an early ventricular premature beat and the failure to restore a normal sinus rhythm by defibrillation are unusual for torsade de pointes and are more consistent with the undulatory phase of ventricular fibrillation. As this case illustrates, it may be difficult to distinguish between a paroxysm of delayed repolarization syndrome that degenerates into ventricular fibrillation and primary or secondary ventricular fibrillation [24]. The history and the electrocardiographic findings after defibrillation are usually sufficient to rule out or confirm delayed repolarization syndrome. If the cause of ventricular fibrillation cannot be established, control of the arrhythmia with bretylium or overdrive pacing should be considered. The third subgroup included three patients in whom torsade de pointes occurred during electrophysiologic study. The first two patients had coronary artery disease and sustained uniform ventricular tachycardia. In both patients, torsade de pointes was initiated by a single ventricular extrastimulus. The third patient (Figure 7) had no identifiable heart disease but underwent an electrophysiologic study because of syncope of un-
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The American Journal of Medicine
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3’A~~‘OS’S
OC F_AYED
REPOLARIZATION
SVNDROME-SCHWEITLW
ana wwn
Figure 6. Patient 3, Table II. Initiation of terminal ventricular fibrillation. The two rhythm strips are continuous. The beginning of the upper strip shows sinus bradycardia (heart rate 52 beats per minute) and a corrected Q-T interval of 0.43 second. The S-T segment of the third sinus beat is interrupted by a ventricular premature beat, which initiates a short run of torsade de pointes. After a single sinus beat, a similar episode reappears that deteriorates into ventricular fibrillation.
known cause. As seen in Figure 7, a burst of ventricular stimuli initiated a self-terminating paroxysm of torsade de pointes. The arrhythmia could be reproduced only 75 percent of the time with burst ventricular stimulation. The clinical significance of torsade de pointes induced during electrophysiologic study depends on the underlying disease and spontaneous arrhythmia. According to Horowitz et al [5], torsade de pointes in patients with a normal Q-T interval and a history of sustained ventricular tachycardia should be managed in the same way as patients with uniform ventricular tachycardia. The significance of short paroxysms of torsade de pointes in patients lacking a history or documentation of a previous episode of ventricular tachycardia is difficult to evaluate and requires further study. Finally, the electrocardiogram in a single patient wlth atrial fibrillation in whom the administration of aminophylline initiated a very rapid, wide QRS complex tachycardia resembling torsade de pointes is illustrated in Figure 8. This patient was admitted to the hospital with lobar pneumonia complicated by atrial fibrillation and bronchospasm. He was treated with aminophylline for the latter. During the infusion of aminophylline, the ventricular rate increased to 300 beats per minute, the
QRS complexes widened and, at the end of the paroxysms, undulation of the QRS complexes was seen. This lasted for four to five seconds and was followed by a short pause after which atrial fibrillation with a slower ventricular rate resumed. We assume that, in this patient, aminophylline facilitated atrioventricular conduction [25] and induced venticular tachycardia. However, aberrant conduction or conduction over atrioventricular nodal bypass tracts cannot be excluded, although there was no evidence of Wolff-Parkinson-White syndrome at any time. The arrhythmia resembled torsade de pointes, but the normal Q-T interval, absence of apparent cause of delayed repolarization syndrome, and the occurrence of a single episode of this arrhythmia during facilitation of atrioventricular conduction suggest that this was not delayed repolarization syndrome. Aminophylline was discontinued and the patient was given dlgoxin. He received no other treatment and the arrhythmia did not reoccur. COMMENTS At this time, there is no uniformly accepted terminology for arrhythmias related to abnormal repolarization. These rhythm disturbances are named either in terms
Ftgure 7. Patient 7, Table II. Torsade de pointes initiated by burst ventricular pacing. From top to bottom, lead I, lead it, high right atria/ (HRA), and right ventricular apex (RV) electrogram. The first ventricular stimulus (S) is ineffective because it occurs during the QRS complex. The next four ventricular stimuli capture the ventricle and initiate a short setf-termination paroxysm of torsade de pointes.
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September 1983
The Amerlcsn Journal of Medlclne
Volume 75
DIAGNOSIS
OF DELAYED REPOLARIZATION
SYNDROME-SCHWEITZER
and MARK
Flgure 8. Patient 8, Table II. A rhythm strip of a monitor lead in a patient with multiform ventricular tachycardia and normal Q-T interval. The strip shows tachycardia with wide and undulating CRS complexes consistent with torsade de pointes. At the mi&portjon of the second strip, the arrhythmia is replaced by atria/ fibrillation and fast ventricular response.
of etiology (e.g., quinidine syncope [12]) or by description, such as torsade de pointes [ 11, polymorphous ventricular tachycardia [ 91, or transient ventricular fibrillation [ 71. The literature contains at least 10 names for this arrhythmia [ 1,7-10,26-261. Probably the main reason that multiple terms have been used to describe delayed repolarization syndrome is the marked variation of the electrocardiographic findings in these patients. At one end of the spectrum are patients with uniform ventricular tachycardia (Figure 4) or typical torsade de pointes (Figure 1) and at the other extreme are those with ventricular fibrillation or flutter (Figure 2). Because these arrhythmias may vary morphologically from patient to patient and from time to time in a single patient, it is preferable to use a term that emphasizes the basic electrophysiologic abnormality. We believe that the term delayedrepolarization syndrome suggested by Reynolds and Vander Ark [ 131 fulfills this requirement and should be used. This approach, however, does not exclude the identification by name of a specific arrhythmia as well. The descriptive terminology of atypical ventricular tachycardia has been further complicated by controversial use of the term torsade de pointes. Krikler and Curry [3] suggested that tomade de pointes be reserved for arrhythmias due to a long Q-T interval and multiform ventricular tachycardia for those with a normal Q-T interval. Other investigators use the term torsade de pointes regardless of the duration of the Q-T interval
[VI. The diagnosis of delayed repolarization syndrome cannot be based only on the analysis of the arrhythmia, but requires confirmation that delayed repolarization is present and determination of its cause. Among the most frequent causes of torsade de pointes and delayed repolarization syndrome are class I ant&rhythmic drugs and hypokalemia [ 18,291. Another common cause of torsade de pointes is marked bradycardia [29]. It can be argued that torsade de pointes due to slow heart rate does not fulfill the criteria for delayed repolarization syndrome because there are no primary abnormalities of ventricular repolarization. We believe, however, that these patients should be included in this group because they have a long, uncorrected Q-T interval and a similar
electrocardiographic appearance, and because they respond to the same treatment as patients with delayed repolarization syndrome due to other causes. The practical significance of correct identification of torsade de pointes and delayed repolarization syndrome and their causes is obvious. The recommended treatment for torsade de pointes due to a long Q-T interval includes isoproterenol and artificial pacing [2,3]. In addition, bretylium is effective in some of these patients [30]. On the other hand, torsade de pointes with a normal Q-T interval may be treated with ant&rhythmic drugs, including those in class I [4,5]. Knowledge that torsade de pointes or similar arrhythmias occur in patients with normal repolarization means that before therapy with isoproterenol is instituted or a temporary pacemaker is inserted, it is necessary to confirm that the arrhythmia is a manifestation of delayed repolarization syndrome. This approach is especially important in patients with coronary artery disease in whom the administration of isoproterenol may be hazardous. Some recent studies [5,6] indicate that coronary artery disease is one of the leading types of underlying heart disease in patients with torsade de pointes with or without a long Q-T interval. According to Zilcher et al [ 61, 62 percent of patients with torsade de pointes had coronary artery disease. Similar findings were reported in patients in whom torsade de pointes was induced during electrophysiologic study [5]. It is also important to note that the duration of the Q-T interval has been shown to be an important prognostic marker for sudden death after acute myocardial infarction [3 1,321. Patients who died suddenly after myocardial infarction as a group had a longer Q-T interval than did survivors. Another important finding is that patients with left ventricular dysfunction are at higher risk for development of delayed repolarization syndrome while receiving quinidine. Denes et al [23] reviewed the incidence of ventricular fibrillation during ambulatory electrocardiographic recording and found that the majority of patients in whom this arrhythmia developed had left ventricular dysfunction and had taken quinidine. In addition, 60 percent of patients with torsade de pointes have been shown to have organic heart disease [5]. However, these assumptions are not generally ac-
September1983 The American Journal of Medicine Volume75
399
DIAGNOSIS OF DELAYED REPOLARIZATION SYNDROME-SCHWEITZER and MARK
cepted.
Velebit
correlation dysfunction, rhythmic
et al
[33] were not able to find a good
between and the
heart
disease,
arrhythmogenic
left effect
ventricular of antiar-
drugs.
Patients prolongation
with
mitral
of the
valve Q-T
prolapse
interval.
may
In fact,
also torsade
show de
has been reported in some of these patients, occurring either spontaneously or following administration of quinidine [ 16,34-361. The exact mechanism causing torsade de pointes remains unclear. The original concept that torsade de pointes is caused by two ectopic foci was reexamined by Bardy et al [37], who found that an experimental arrhythmia resembling torsade de pointes was due to two or more ectopic foci. In a report by Lazzara et al [38], one patient with a long Q-T interval demonstrated large afterpotentials, which were the source of ventricular premature beats during the administration of epinephrine. This study supports the hypothesis that an ectopic focus could be the basis for the arrhythmia occurring in the long Q-T interval syndrome. Reentry as a mechanism is supported by studies in which torsade de pointes was initiated by ventricular extrastimulation 139,401. The relationship between idiopathic or congenital and pointes
acquired long Q-T interval syndrome is also unclear. The autonomic nervous system seems to play an important role in the pathogenesis of the congenital form of the long Q-T interval syndrome [ 161. In these patients, the arrhythmia cannot be initiated by venticular stimulation [41] and the administration of catecholamines may have adverse effects. Beta blockade, phenytoin, and phenobarbital have been used to reduce the risk of arrhythmias in patients with the congenital long Q-T syndrome. In those patients refractory to these drugs, left cervicothoracic sympathetic ganglionectomy has been recommended [ 161. In the acquired form of the long Q-T interval syndrome, the rhythm disturbance can be initiated by ventricular stimulation [40] and catecholamines may control the arrhythmia. Because of the noted different response to drugs, it is important to distinguish between the congenital and acquired form of the long Q-T interval syndrome. In the majority of patients, history alone is sufficient to differentiate between various forms of the long Q-T interval syndrome. However, difficulties in distinguishing between the congenital and acquired type of delayed repolarization syndrome may arise in patients who have latent Q-T interval prolongation that is unmasked by the administration of certain drugs [42,43].
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a. 9.
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466
Dessertenne F: La tachycardie ventriculaire a deux foyers opposes variables. Arch Mal Coeur 1966; 52: 263-272. Brochier M, Motte G, Fauchier JP: Tachycardie venticulaire en torsades de pointe. Actual Cardiovasc Med Chirurg 1972; 6: 171-194. Krikler DM, Curry PVL: Torsade de pointes, an atypical ventricular tachycardia. Br Heart J 1976; 38: 117-120. Slama R, Coumel P, Matte G. et al: Tachycardies ventriculaires et torsades de pointes. Frontieres morphologiques entre les dysrhythmies ventriculaires. Arch Mal Couer 1973; 66: 1401-1411. Horowitz LN, Greenspan AM, Spelman SR, Josephson ME: Torsade de pointes: electrophysiologic studies in patients without transient pharmacologic or metabolic abnormalities. Circulation 1981; 63: 1120-l 128. Zilcher H, Glogar D, Kaindl F: Torsade de pointes; occurrence in myocardial ischemia as a separate entity. Multiform ventricular tachycardia or not? Eur Heart J 1980; 1: 6371. Schwartz SP, Jezer A: The action of quinine and quinidine in patients with transient ventricular fibrillation. Am Heart J 1934; 9: 792-801. Ranquin R, Rarizel G: Ventricular fibrillo-flutter (“torsade de pointe”): an estblished electrocardiographic and clinical entity. Angiology 1977; 28: 115-l 18. Sclarovsky S, Strasberg B, Lewin RF, Agmon J: Polymorphous ventricular tachycardia. Clinical features and treatment. Am J Cardiol 1979; 44: 339-344. Loeb HS, Pietras RJ, Gunnar RM, Tobin R Jr: Paroxysmal ventricular fibrillation in two patients with hypomagnesemia. Circulation 1968; 36: 210-215. Keren A, Tzivoni D, Gavish D, et al: Etiology, warning signs
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1963
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Volume 75
and therapy of torsade de pointes. A study of ten patients. Circulation 1981; 64: 1167-l 174. Seizer A, Wray HW: Quinidine syncope. Paroxysmal ventricular fibrillation occurring during treatment of chronic atrial arrhythmias. Circulation 1964; 30: 17-26. Reynolds EW, Vander Ark CR: Quinidine syncope and the delayed repolarization syndromes. Mod Concepts Cardiovast Dis 1976; 45: 117-122. Smith WM, Gallagher JJ: “Les torsades de pointes.” An unusual ventricular arrhythmia. Ann Intern Med 1980; 93: 578-584. Moss AJ, Schwartz PJ: Sudden death and the idiopathic long QT syndrome. Am J Med 1979; 66: 6-7. Moss AJ, Schwartz PJ: Delayed repolarization (QT or QTU prolongation) and malignant ventricular arrhythmias. Mod Concepts Cardiovasc Dis 1982; 51: 85-90. Lepeschkin E: The U wave of the electrocardiogram. Mod Concepts Cardiovasc Dis 1969; 38: 39-45. Matte G, Coumel P, Abitol G, et al: Le syndrome QT long et syncopes part “torsades de pointe.” Arch Mal Coeur 1970; 63: 831-853. Schamroth L: The disorders of cardiac rhythm. Oxford: Blackwell Scientific Publications, 1971; 109. Watanabe Y, Dreifus LS: Cardiac arrhythmias: electrophysiologic basis for clinical interpretation. New York: Grune 8 Stratton, 1977; 254. Strasberg B, Sclarovsky S, Erdberg A, et al: Procainamideinduced polymorphous ventricular tachycardia. Am J Cardiol 1981; 47: 1309-1314. Mallion JM, Avezou F, Denis B, Yaccoub M, Martin-Noel P: Syndrome de QT long avec torsades de pointes. syncope et insuffisance coronarieene. Arch Mal Coeur 1971; 65:
DIAGNOSIS
23.
24.
25.
26.
27.
28.
29.
30.
31.
32.
33.
1209-1214. Denes P, Gabster A, Huang SK: Clinical, electrocardiographic and follow-up observations in patients having ventricular fibrillation during Holter monitoring. Role of quinidine therapy. Am J Cardiol 1981; 48: 9-16. Kossman CE: Torsade de pointes: an addition to the nosography of ventricular tachycardia. Am J Cardiol 1978; 42: 1054-1056. Greenberg HB, Antin SH: 1: 1 conduction in atrial flutter after intravenous injection of aminophylline. J Electrocardiol 1972; 5: 391-393. Scherf D, Cohen J, Shafilha H: Ectopic ventricular tachycardia, hypokalemia and convulsion in alcoholics. Cardiologia 1967; 50: 129-139. MacWilliam JA: Some application of physiology to medicine. II. Ventricular fibrillation and sudden death. Br Med J 1923; 2: 215-219, Smirk FH, Ng J: Cardiac ballet: repetitions of complex electrocardiographic patterns. Br Heart J 1969; 31: 426434. Fontaine G, Frank R, Grosgogeat Y: Torsade de pointes: definition and management. Mod Concepts Cardiovasc Dis 1982; 51: 103-108. Vander Ark CR, Reynolds EW, Kahn DR, Tullett G Quinidine syncope. A report of successful treatment with bretylium tosylate. J Thorac Cardiovasc Surg 1976; 72: 464-467. Schwartz PJ, Wolf S: QT interval prolongation as predictor of sudden death in patients with myocardial infarction. Circulation 1978; 57: 1074-1077. Ahnve S, Lundman T, Shoaleh-Var M: The relationship between QT interval and ventricular arrhythmias in acute myocardial infarction. Acta Med Stand 1978; 204: 1719. Velebit V, Podrid P, Lown B, et al: Aggravation and provocation of ventricular arrhythmias by antiarrhythmic drugs. Circu-
OF DELAYED REPOLARIZATION
34. 35.
36.
37.
38.
39.
40.
41.
42.
43.
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SYNDROME-SCHWEITSIER
and MARK
lation 1982; 65: 886-894. Bekheit S, Ali A: QT interval in idiopathic prolapsed mitral valve (abstr). Am J Cardiol 1978; 41: 374. Wei JY. Bulkley BH, Schaeffer AH, Greene H, Reid PR: Mitral-valve prolapse syndrome and recurrent ventricular tachyarrhythmias. A malignant variant refractory to conventional drug therapy. Ann Intern Med 1978; 89: 6-9. Campbell RW, Godman MG. Fiddler GI. et al: Ventricular arrhythmias in syndrome of balloon deformity of mitral valve. Definition of possible high risk group. Br Heart J 1976; 38: 1053-1057. Bardy GH, Ungerleider RM, Smith WM, et al: A mechanism of torsade de pointes as observed in a dog model (abstr). Circulation 1981; 64 (suppl IV): IV-218. Lazzara R, Hope RR, Freeman CC, et al: After potentials as a cause of long QT syndrome? Electrophysiological study of a case (abstr). Am J Cardiol 1980; 45: 472. Fontaine GH, Frank R, Welti JJ, Grosgogeat Y: Electrophysiology of torsade de pointes. In: Meere C, ed. Proceedings of the Vlth World Symposium on Cardiac Pacing. Montreal: Pacesym, 1979: 3. Evans TR. Curry PVL, Fitchett DH, Kirkler MM: “Torsade de pointes” initiated by electrical ventricular stimulation. J Electrocardiol 1976; 9: 255-258. Hartzler GO, Osborn MJ: Invasive electrophysiological study in the Jervel and Lange-Nielsen syndrome. Br Heart J 1981; 45: 225-229. Koster KW, Wellens HJJ: Quinidine-induced ventricular flutter and fibrillation without digitalis therapy. Am J Cardiol 1976; 38: 519-523. Schneider RR, Bahler A, Pincus J, et al: Asymptomatic idiopathic syndrome of prolonged QT interval in a 45year-old woman. Ventricular tachyarrhythmias precipitated by hypokalemia and therapy with amitriptyline and perpenazine. Chest 1977; 71: 210-213.
The American Journal of Medicine
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PAUL SCHWEITZER, M.D. HERBERT MARK, M.D. New York, New York
From the Cardiology Section, Department of Medicine, Veterans Administration. Hospital, Bronx, New York, and the Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine, New York, New York. Requests for reprints should be addressed to Dr. Paul Schweitzer, Cardiology Section, Veterans Administration Hospital, 130 West Kingsbridge R&d, Bronx, New York 10466. Manuscript accepted January 27, 1963.
The electrocardiograms of 18 patients with atypical ventricular tachycardia manifested as torsade de pointes, ventricular fibrilloflutter, polymorphous ventricular tachycardia, and uniform ventricular tachycardia were analyzed. The patients were divided into two groups: The first group included 10 patients with prolonged 0-T intervals or abnormal U waves (delayed repolarization) and the second group included eight patients with normal ventricular repolarization. All of the electrocardiographic manifestations of atypical ventricular tachycardia were seen In both groups, regardless of the duration of the Q-T interval or the presence of an abnormal U wave. It is suggested that QRS morphology during the tachycardia is not sufficient to distinguish between delayed repolarization and other causes of atypical ventricular tachycardia. Finally, because the electrocardiogram may vary among different patients and from one episode to the next in a single patient due to abnormal repolarizatlon, it is recommended that the term de/ayed repolarizafion syndrome be used to identify the arrhythmia. In 1966, Dessertenne [l] described torsade de pointes, an atypical ventricular tachycardia that was characterized by continuous change in the direction of the ventricular complexes of the electrocardiogram. Because the majority of patients with torsade de pointes described since that report have a long Q-T interval, it was suggested by some investigators [2,3] that this arrhythmia is pathognomic of delayed repolarization [4-61. According to Slama and co-workers [4] and others [5,6], torsade de pointes also occurs in patients with normal Q-T intervals. On the other hand, not all arrhythmias associated with a prolonged Q-T interval fulfill the criteria for torsade de pointes. In some patients, the rhythm disturbance is suggestive of ventricular fibrillation [ 7,8], while others demonstrate a beat-to-beat variation in the morphology of the QRS complexes [9]. The variability of the electrocardiographic features explains why this arrhythmia has also been referred to as transient [7] or paroxysmal ventricular fibrillation [ lo], polymorphous ventricular tachycardia [ 91, or atypical ventricular tachycardia [ 111. Some investigators prefer an etiologic rather than an electrocardiographic diagnosis, e.g., quinidine syncope [ 121. Reynolds and Vander Ark [ 131, emphasizing the underlying electrophysiologic abnormality, recommended the term delayed repolarization syndrome that will be used in this study. In recent years, an increased number of studies dealing with different aspects of torsade de pointes have been reported. Although some of these reports defined the cause, established diagnostic criteria, and suggested an approach to management of torsade de
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DIAGNOSIS OF DELAYED REPOLARIZATION SYNDROME-SCHWEITZER and MARK
TABLE I
Data on Patients with Delayed Repolarization Syndrome Corrected O-T Interval (seconds)
Cause of Delayed Repolarization Syndrome
Patient Number
Age (Yr)
1 2 3 4
20 48 65 56
0.63 0.56 0.62 0.52
No heart disease Hypertension Coronary artery disease Acute myocardial infarction
? Idiopathic Quinidine Quinidine Procainamide
5
48
0.62
Schizophrenia
Chlorpromazine
6
63
0.54
Quinidine
7 8
84 54
0.52
Chronic obstructive lung disease Atrioventricular block Acute myocardial infarction
9
45
0.52
10
56
0.48
Clinical Diagnosis
Coronary artery disease, ventricular aneurysm Chronic obstructive lung disease
APB = atrial premature beats; VPB = ventricular
Bradycardia Acute myocardial infarction Disopyramide, hypokalemia Quinidine, hypokalemia
premature beats; VT = ventricular
pointes, others contributed to the confusion surrounding the syndrome [l-3,5,6,14]. Whether the term torsade de pointes should be reserved solely for arrhythmias with prolonged Q-T intervals or should be also used for patients with normal Q-T intervals [3,5,6] is a question that has remained unsolved. The purpose of this study is to analyze the electrocardiographic manifestation of malignant ventricular arrhythmias in patients with prolonged Q-T intervals and to reassess the usefulness and the limitation of the electrocardiogram in the differentiation of atypical ventricular tachycardia with normal and long Q-T intervals.
Therapy Propranolol Lidocaine Lidocaine Lidocaine, cardioversion, propranolol Lidocaine, cardioversion Bretylium, pacing
APB and VPB Nonsustained VT
Nonsustained VT
Pacing Bretylium Nonsustained VT
Bretylium, potassium Potassium
Atrial tachycardia tachycardia.
PATIENTS AND METHODS We analyzed the clinical and electrocardiographic findings in 18 patients with atypical ventricular tachycardia. In IO patients the arrhythmia was due to delayed repolarization syndrome, while eight patients had normal or nearly normal Q-T intervals. The age of these patients, their clinical diagnoses, the cause of the rhythm disturbances, and treatment are summarized in Tables I and II.
The most important diagnostic feature of delayed repolarization syndrome is a corrected Q-T interval for heart rate in excess of 0.44 seconds [is] or an uncorrected one measuring 0.50 second or more [ 1 l] According to Moss and Schwartz [ 161, another marker of delayed repolarization is
Data on Patients with Normal Ventricular Repolarization
TABLE II
Corrected Q-T Interval lsecondsl
Patient Number
Age fvr)
1
62
0.48
Cardiomyopathy
2
38
0.43
Cardiomyopathy
3 4
54 72
0.43 0.45
Acute myocardial infarction Acute myocardial infarction
5
56
0.42
Coronary artery disease
6
62
0.40
Coronary artery disease
7
57
0.38
7 Syncope
a
73
0.41
Pneumonia, atrial fibrillation
394
Indication for Antiarrhythmic Drugs
September
1993
Clinical Diagnosis
The American
Journal
of Medicine
Tvpe of Ventricular Bachvcardia Polymorphous ventricular tachycardia Polymorphous ventricular tachycardia Torsade de pointes Torsade de pointes, ventricular fibrillo-flutter Torsade de pointes during electrophysiologic study Torsade de pointes during electrophysiologic study Torsade de pointes during electrophysiologic study Torsade de pointes
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Theraw Procainamide,
digoxin
Procainamide,
digoxin
Defibrillation (unsuccessful) Defibrillation, lidocaine Procainamide Procainamide No therapy Digoxin
DIAGNOSIS
an abnormal bifid or sinusoidal T wave. The measurement of the Q-T interval and its differentiation from the U wave may be difficult or impossible in the latter instance. One way to distinguish a bifid T wave from a TU wave is to measure the interval between the two peaks [ 171. An interval 0.15 second or less is consistent with a bifid T wave, and one exceeding 0.15 second suggests that the second peak is a U wave. Differentiation between the T and U wave can be achieved by simultaneous recording of an electrocardiogram and phonocardiogram [ 171. The beginning of the U wave coincides with the second heart sound. Phonocardiography, however, is rarely performed in acutely ill patients and this method is probably of limited practical significance. As noted, delayed repolarization may be diagnosed in patients with long Q-T intervals or in those with abnormal U waves. Diagnostic features of an abnormal U wave have not been fully defined. According to Lepeschkin [ 171, the U wave in the standard limb leads is 0.05 mV or less in 95 to 97 percent of normal subjects, while the amplitude of the U wave in the precordial leads has an upper limit of 0.3 mV. The presence of a prominent U wave or alternation of its amplitude are consistent with delayed repolarization syndrome. The electrocardiographic manifestation of delayed repolarization syndrome varies, and may appear as any of the following arrhythmias. 1. Torsade de pointes [ l-3,14,18]. This arrhythmia is characterized by marked changes in the amplitude and the direction of the vector of the ventricular complex, giving the impression that the QRS complex is twisting around an imaginary baseline. The heart rate varies between 150 and 300 beats per minute and the rhythm is irregular. Paroxysms of torsade de pointes are usually initiated by a late occurring ventricular extrasystole or may be preceded by ventricular couplets or triplets. Sometimes it is necessary to record multiple leads to diagnose torsade de pointes, because the more frequent uniform ventricular tachycardia may be simulated if only a single electrocardiographic lead is recorded. 2. Ventricular fibrillo-flutter [8,19]. This arrhythmia consists of runs of ventricular flutter interrupted by fibrillation. 3. Uniform ventricular tachycardia or ventricular flutter. Bizarre ventricular complexes that fuse with the ST-T segment characterize this arrhythmia. The amplitude of the ventricular deflection is uniform, unlike torsade de pointes. However, differentiation between ventricular tachycardia and ventricular flutter may be difficult, and no clear-cut criteria for their separation have been proposed [ 19,201. A more rapid rate and a transient nature are probably more consistent findings in ventricular flutter than in ventricular tachycardia. Ventricular flutter usually progresses rapidly into ventricular fibrillation. 4. Polymorphous or multiform ventricular tachyardia [ 91. In this arrhythmia, the heart rate varies between 150 and 300 beats per minute and the ventricular deflection changes from beat to beat. Identification of these electrocardiographic manifestations of delayed repolarization syndrome may not always be possible because a change from one configuration to another occurs commonly and is probably itself one of the characteristics of delayed repolarization syndrome.
OF DELAYED REPOLARIZATION
SYNDROME-SCHWEITZER
and MARK
Figure 1. Patient 1, Table 1.Rhythm strip of lead II. The first strip shows regular sinus rhythm and notched T wave with a corrected Q-T interval of 0.63 second. In the second strip, the sinus beats are followed by multiform ventricular extrasystoles and tachycardia. The third and fourth strips are continuous, demonstrating multiform ventricular premature beats and a paroxysm of torsade de pointes.
RESULTS
Delayed Repolarization Syndrome. Clinical data, including the cause of delayed repolarization syndrome, and previous treatment in our 10 patients are presented in Table I. The cause of delayed repolarization syndrome could not be determined in only one patient (Patient 1). The syndrome and associated arrhythmias could be attributed to administration of a single medication in five patients (Patients 2 to 6) and to underlying complete atrioventricular block in another (Patient 7). Patient 8 had an acute myocardial infarction. In two patients (Patients 9 and lo), at least two predisposing causes of delayed repolarization syndrome were present. Both patients were taking class I antiarrhythmic drugs and were hypokalemic. The electrocardiographic manifestations of delayed repolarization syndrome differ in individual patients and ’ may also vary from time to time in a single patient (Figures 1 to 4). The diagnostic criteria for torsade de pointes are fulfilled in Figure 1 (Patient l), which shows a self-terminating episode of torsade de pointes and late multiform ventricular extrasystoles. The variability of the electrocardiogram recorded in a patient with complete atrioventricular block and malfunctioning permanent pacemaker is shown in Figure 2. This patient experienced multiple paroxysms of delayed repolarization syndrome; some appeared as typical torsade de pointes (Figure 2A) and others as ventricular flutterfibrillation, requiring defibrillation (Figure 2C and D). The next case demonstrates some of the difficulties encountered in the diagnosis of delayed repolarization syndrome. The electrocardiogram was recorded in a patient with extensive acute anterior myocardial infarction (Patient 4). The patient had been treated with procainamide for nonsustained ventricular tachycardia
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DIAGNOSIS
Figure 2. Patient 7, Table 1.Rhythm strip of lead II. The underlying rhythm is atrial fibrillation, and the baseline is interrupted by ineffective pacemaker spikes. Strip A shows torsade de pointes and multiform ventricular extrasystoles; the latter are also seen in strip B. Strip C starts with well-defined QRS complexes followed by torsade de pointes. Strip D is consistent with ventricular fibrillo-flutter.
Figure 3. Patient 4, Table I. The rhythm strip is from a 24hour ambulatory electrocardiographic recording of lead V, and VI. The corrected O-T interval measures 0.52 second. In strip A (V,), the sinus rhythm is interrupted by ventricular extrasystoles and a paroxysm of ventricular tachycardia. At the beginning of the tachycardia, the main ventricular deflections are negative, then decrease in amplitude after a few beats and become positive. In lead VI, the QRS complexes are uniform and of small amplitude. In both leads of strip 8, there is uniform ventricular tachycardia.
I
I
Patient 5, Table 1.Rhythm strip of a monitor lead. The corrected Q-T interval measures 0.62 second. At the beginning of tha strip, the sinus beats alternate with multiform ventricular extrasystoles, followed by uniform ventricular tachycardia.
Figure 4.
(6 grams given in divided doses over 24 hours). During the administration of the drug, the corrected Q-T interval increased from 0.42 to 0.52 second. Although the ventricular complexes in V5 resembled torsade de pointes, those in lead VI were uniform and of low voltage (Figure 3A). After 30 seconds, this arrhythmia de-
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generated into ventricular fibrillation, requiring defibrillation. Following this episode, the patient was treated with lidocaine, which temporarily controlled the rhythm disturbance. The tachycardia recurred 45 minutes later, but in this episode the QRS deflection was morphologically uniform in both leads (Figure 3B). Alternating paroxysms of multiform and uniform tachycardia were recorded over the succeeding two to three hours, during which time propranolol was also administered. Finally, the arrhythmia became refractory to lidocaine and propranolol and the patient died. It was assumed that the arrhythmia was caused by the underlying disease rather than by procainamide, because oral administration of this drug rarely causes delayed repolarization syndrome [21]. Rapid degeneration of the ventricular tachycardia into ventricular fibrillation also supported this explanation. However, it is also possible that the
Volume 75
DIAONO~IS OF DELAYED REPOLARIZATIONSYNDROME--SCHWEITZER and MARK
patient had delayed repolarization syndrome, caused by acute myocardial infarction [6,22] and procainamide. The electrocardiogram shown in Figure 4 (Patient 5) also demonstrates that delayed repolarization syndrome can rapidly degenerate into ventricular fibrillation. This patient was admitted to the cardiac care unit for observation because an electrocardiogram taken after he had experienced dizziness revealed a prolonged Q-T interval and multiform ventricular premature beats. This patient had been treated with chlorpromazine. Subsequently, a paroxysm of uniform ventricular tachycardia was recorded, which rapidly deteriorated into ventricular fibrillation, which was successfully treated with direct current countershock. The arrhythmia seemed to be uniform, however, because only a single lead was recorded multiform ventricular tachycardia, or torsade de pointes cannot be excluded. Lidocaine was given subsequently, and there were no recurrences of ventricular tachycardia. Atypical Ventricular Tachycardia with Normal Repolarization. The diagnoses, electrocardiographic findings, and the type of treatment given to eight patients without delayed repolarization syndrome in whom the arrhythmia resembled torsade de pointes or another atypical ventricular tachycardia are listed in Table II. These eight patients form a nonhomogeneous group that can be divided into four subgroups. The first subgroup comprises two patients with cardiomyopathy and severe congestive heart failure. When the electrocardiogram of Patient 1 (Figure 5A) was taken, the patient had normal levels of blood electrolytes and was receiving digoxin and furosemide. The corrected Q-T interval measured 0.48 second and short episodes of polymorphous ventricular tachycardia were noted. Despite the fact that this patient had a slightly prolonged Q-T interval, he was given procainamide, which controlled the arrhythmia (Figure 58) and had no further effect on the Q-T interval. Probably the most important findings that help to exclude delayed repolarization syndrome in this type of patient are the subacute or chronic nature of the arrhythmia and the absence of a cause of delayed repolarization syndrome. However, diagnostic difficulties may arise if the patient is treated with antiarrhythmic drugs. There is a greater risk of malignant ventricular arrhythmia developing in patients with impaired left ventricular function during treatment with quinidine [23]. Accordingly, worsening of a ventricular arrhythmia during the administration of quinidine or another antiarrhythmic drug should raise the possibility of delayed repolarization syndrome. In the second subgroup were two patients with coronary artery disease and ventricular fibrillation. The initial phase of ventricular fibrillation resembled torsade de pointes _inboth of these patients.
Figure 5.
Patient 1, Table II. Two rhythm strips (V2 and V,) in a patient with multiform ventricular tachycardia. The corrected Q-T interval measures 0.48 second. In strip A (V,), sinus rhythm at a rate of 115 beats per minute and polymorphous ventricular tachycardia are seen. Strip 6, which was recorklafter the patient was treated with procainami&, shows regular sinus rhythm and a late ventricular extrasysto/e. The corrected Q-T interval remained unchanged.
The electrocardiogram in Figure 6 was recorded in a patient with acute myocardial infarction. This patient had been taking propranolol for angina pectoris (160 mg per 24 hours) but no class I antiarrhythmic drug. Serum potassium level was normal. Sinus bradycardia was present and the corrected Q-T interval measured 0.43 second. The sinus bradycardia was interrupted by an early ventricular premature beat, which initiated a paroxysm of torsade de pointes. After a single sinus beat, the arrhythmia reappeared and rapidly degenerated into ventricular fibrillo-flutter. Repeat defibrillation failed to restore sinus rhythm and the patient died. The initial paroxysm, which terminated spontaneously, fulfills the diagnostic criteria for torsade de pointes. The slow heart rate and the recent myocardial infarction favored this diagnosis. However, the initiation of the ventricular arrhythmia by an early ventricular premature beat and the failure to restore a normal sinus rhythm by defibrillation are unusual for torsade de pointes and are more consistent with the undulatory phase of ventricular fibrillation. As this case illustrates, it may be difficult to distinguish between a paroxysm of delayed repolarization syndrome that degenerates into ventricular fibrillation and primary or secondary ventricular fibrillation [24]. The history and the electrocardiographic findings after defibrillation are usually sufficient to rule out or confirm delayed repolarization syndrome. If the cause of ventricular fibrillation cannot be established, control of the arrhythmia with bretylium or overdrive pacing should be considered. The third subgroup included three patients in whom torsade de pointes occurred during electrophysiologic study. The first two patients had coronary artery disease and sustained uniform ventricular tachycardia. In both patients, torsade de pointes was initiated by a single ventricular extrastimulus. The third patient (Figure 7) had no identifiable heart disease but underwent an electrophysiologic study because of syncope of un-
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3’A~~‘OS’S
OC F_AYED
REPOLARIZATION
SVNDROME-SCHWEITLW
ana wwn
Figure 6. Patient 3, Table II. Initiation of terminal ventricular fibrillation. The two rhythm strips are continuous. The beginning of the upper strip shows sinus bradycardia (heart rate 52 beats per minute) and a corrected Q-T interval of 0.43 second. The S-T segment of the third sinus beat is interrupted by a ventricular premature beat, which initiates a short run of torsade de pointes. After a single sinus beat, a similar episode reappears that deteriorates into ventricular fibrillation.
known cause. As seen in Figure 7, a burst of ventricular stimuli initiated a self-terminating paroxysm of torsade de pointes. The arrhythmia could be reproduced only 75 percent of the time with burst ventricular stimulation. The clinical significance of torsade de pointes induced during electrophysiologic study depends on the underlying disease and spontaneous arrhythmia. According to Horowitz et al [5], torsade de pointes in patients with a normal Q-T interval and a history of sustained ventricular tachycardia should be managed in the same way as patients with uniform ventricular tachycardia. The significance of short paroxysms of torsade de pointes in patients lacking a history or documentation of a previous episode of ventricular tachycardia is difficult to evaluate and requires further study. Finally, the electrocardiogram in a single patient wlth atrial fibrillation in whom the administration of aminophylline initiated a very rapid, wide QRS complex tachycardia resembling torsade de pointes is illustrated in Figure 8. This patient was admitted to the hospital with lobar pneumonia complicated by atrial fibrillation and bronchospasm. He was treated with aminophylline for the latter. During the infusion of aminophylline, the ventricular rate increased to 300 beats per minute, the
QRS complexes widened and, at the end of the paroxysms, undulation of the QRS complexes was seen. This lasted for four to five seconds and was followed by a short pause after which atrial fibrillation with a slower ventricular rate resumed. We assume that, in this patient, aminophylline facilitated atrioventricular conduction [25] and induced venticular tachycardia. However, aberrant conduction or conduction over atrioventricular nodal bypass tracts cannot be excluded, although there was no evidence of Wolff-Parkinson-White syndrome at any time. The arrhythmia resembled torsade de pointes, but the normal Q-T interval, absence of apparent cause of delayed repolarization syndrome, and the occurrence of a single episode of this arrhythmia during facilitation of atrioventricular conduction suggest that this was not delayed repolarization syndrome. Aminophylline was discontinued and the patient was given dlgoxin. He received no other treatment and the arrhythmia did not reoccur. COMMENTS At this time, there is no uniformly accepted terminology for arrhythmias related to abnormal repolarization. These rhythm disturbances are named either in terms
Ftgure 7. Patient 7, Table II. Torsade de pointes initiated by burst ventricular pacing. From top to bottom, lead I, lead it, high right atria/ (HRA), and right ventricular apex (RV) electrogram. The first ventricular stimulus (S) is ineffective because it occurs during the QRS complex. The next four ventricular stimuli capture the ventricle and initiate a short setf-termination paroxysm of torsade de pointes.
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September 1983
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DIAGNOSIS
OF DELAYED REPOLARIZATION
SYNDROME-SCHWEITZER
and MARK
Flgure 8. Patient 8, Table II. A rhythm strip of a monitor lead in a patient with multiform ventricular tachycardia and normal Q-T interval. The strip shows tachycardia with wide and undulating CRS complexes consistent with torsade de pointes. At the mi&portjon of the second strip, the arrhythmia is replaced by atria/ fibrillation and fast ventricular response.
of etiology (e.g., quinidine syncope [12]) or by description, such as torsade de pointes [ 11, polymorphous ventricular tachycardia [ 91, or transient ventricular fibrillation [ 71. The literature contains at least 10 names for this arrhythmia [ 1,7-10,26-261. Probably the main reason that multiple terms have been used to describe delayed repolarization syndrome is the marked variation of the electrocardiographic findings in these patients. At one end of the spectrum are patients with uniform ventricular tachycardia (Figure 4) or typical torsade de pointes (Figure 1) and at the other extreme are those with ventricular fibrillation or flutter (Figure 2). Because these arrhythmias may vary morphologically from patient to patient and from time to time in a single patient, it is preferable to use a term that emphasizes the basic electrophysiologic abnormality. We believe that the term delayedrepolarization syndrome suggested by Reynolds and Vander Ark [ 131 fulfills this requirement and should be used. This approach, however, does not exclude the identification by name of a specific arrhythmia as well. The descriptive terminology of atypical ventricular tachycardia has been further complicated by controversial use of the term torsade de pointes. Krikler and Curry [3] suggested that tomade de pointes be reserved for arrhythmias due to a long Q-T interval and multiform ventricular tachycardia for those with a normal Q-T interval. Other investigators use the term torsade de pointes regardless of the duration of the Q-T interval
[VI. The diagnosis of delayed repolarization syndrome cannot be based only on the analysis of the arrhythmia, but requires confirmation that delayed repolarization is present and determination of its cause. Among the most frequent causes of torsade de pointes and delayed repolarization syndrome are class I ant&rhythmic drugs and hypokalemia [ 18,291. Another common cause of torsade de pointes is marked bradycardia [29]. It can be argued that torsade de pointes due to slow heart rate does not fulfill the criteria for delayed repolarization syndrome because there are no primary abnormalities of ventricular repolarization. We believe, however, that these patients should be included in this group because they have a long, uncorrected Q-T interval and a similar
electrocardiographic appearance, and because they respond to the same treatment as patients with delayed repolarization syndrome due to other causes. The practical significance of correct identification of torsade de pointes and delayed repolarization syndrome and their causes is obvious. The recommended treatment for torsade de pointes due to a long Q-T interval includes isoproterenol and artificial pacing [2,3]. In addition, bretylium is effective in some of these patients [30]. On the other hand, torsade de pointes with a normal Q-T interval may be treated with ant&rhythmic drugs, including those in class I [4,5]. Knowledge that torsade de pointes or similar arrhythmias occur in patients with normal repolarization means that before therapy with isoproterenol is instituted or a temporary pacemaker is inserted, it is necessary to confirm that the arrhythmia is a manifestation of delayed repolarization syndrome. This approach is especially important in patients with coronary artery disease in whom the administration of isoproterenol may be hazardous. Some recent studies [5,6] indicate that coronary artery disease is one of the leading types of underlying heart disease in patients with torsade de pointes with or without a long Q-T interval. According to Zilcher et al [ 61, 62 percent of patients with torsade de pointes had coronary artery disease. Similar findings were reported in patients in whom torsade de pointes was induced during electrophysiologic study [5]. It is also important to note that the duration of the Q-T interval has been shown to be an important prognostic marker for sudden death after acute myocardial infarction [3 1,321. Patients who died suddenly after myocardial infarction as a group had a longer Q-T interval than did survivors. Another important finding is that patients with left ventricular dysfunction are at higher risk for development of delayed repolarization syndrome while receiving quinidine. Denes et al [23] reviewed the incidence of ventricular fibrillation during ambulatory electrocardiographic recording and found that the majority of patients in whom this arrhythmia developed had left ventricular dysfunction and had taken quinidine. In addition, 60 percent of patients with torsade de pointes have been shown to have organic heart disease [5]. However, these assumptions are not generally ac-
September1983 The American Journal of Medicine Volume75
399
DIAGNOSIS OF DELAYED REPOLARIZATION SYNDROME-SCHWEITZER and MARK
cepted.
Velebit
correlation dysfunction, rhythmic
et al
[33] were not able to find a good
between and the
heart
disease,
arrhythmogenic
left effect
ventricular of antiar-
drugs.
Patients prolongation
with
mitral
of the
valve Q-T
prolapse
interval.
may
In fact,
also torsade
show de
has been reported in some of these patients, occurring either spontaneously or following administration of quinidine [ 16,34-361. The exact mechanism causing torsade de pointes remains unclear. The original concept that torsade de pointes is caused by two ectopic foci was reexamined by Bardy et al [37], who found that an experimental arrhythmia resembling torsade de pointes was due to two or more ectopic foci. In a report by Lazzara et al [38], one patient with a long Q-T interval demonstrated large afterpotentials, which were the source of ventricular premature beats during the administration of epinephrine. This study supports the hypothesis that an ectopic focus could be the basis for the arrhythmia occurring in the long Q-T interval syndrome. Reentry as a mechanism is supported by studies in which torsade de pointes was initiated by ventricular extrastimulation 139,401. The relationship between idiopathic or congenital and pointes
acquired long Q-T interval syndrome is also unclear. The autonomic nervous system seems to play an important role in the pathogenesis of the congenital form of the long Q-T interval syndrome [ 161. In these patients, the arrhythmia cannot be initiated by venticular stimulation [41] and the administration of catecholamines may have adverse effects. Beta blockade, phenytoin, and phenobarbital have been used to reduce the risk of arrhythmias in patients with the congenital long Q-T syndrome. In those patients refractory to these drugs, left cervicothoracic sympathetic ganglionectomy has been recommended [ 161. In the acquired form of the long Q-T interval syndrome, the rhythm disturbance can be initiated by ventricular stimulation [40] and catecholamines may control the arrhythmia. Because of the noted different response to drugs, it is important to distinguish between the congenital and acquired form of the long Q-T interval syndrome. In the majority of patients, history alone is sufficient to differentiate between various forms of the long Q-T interval syndrome. However, difficulties in distinguishing between the congenital and acquired type of delayed repolarization syndrome may arise in patients who have latent Q-T interval prolongation that is unmasked by the administration of certain drugs [42,43].
REFERENCES
5.
6.
7.
a. 9.
10.
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