Download Polymorphous ventricular tachycardia: clinical

THERAPY AND PREVENTION
VENTRICULAR TACHYCARDIA
Polymorphous ventricular tachycardia: clinical
characterization, therapy, and the QT interval
PHuC TITo NGUYEN, B.S., MELVIN M. SCHEINMAN, M.D.,
AND
JOHN SEGER, M.D.
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ABSTRACT Forty-five consecutive patients with polymorphous ventricular tachycardia (PVT) were
studied. The arrhythmia proved to be of a drug-related cause in 27 and due to an electrolyte disorder in
four patients. Coexistent cardiac diseases without metabolic or drug-related abnormalities included
ischemic heart disease in three, cardiomyopathy in three, and mitral valve prolapse in two. PVT was
exercise-induced in four and associated with bradyarrhythmias in two. A prolonged QT or corrected
QT interval was inconsistently related to the occurrence of PVT. In patients in whom PVT was induced
by certain type I drugs, other type I antiarrhythmic drugs were usually either ineffective or resulted in
aggravation of arrhythmia. For the group as a whole, treatment with lidocaine resulted in inconsistent
beneficial effects, while cardiac pacing was almost universally effective for those with drug-induced
PVT, regardless of the length of the QT interval. Long-term amiodarone therapy proved safe and
effective for 12 of the 24 patients with drug-induced PVT who required long-term therapy for their
original arrhythmia. We conclude that identification of PVT is the key clinical issue and that the QT
interval is not necessarily the prime abnormality nor the variable to be considered in predicting success
of therapy. Temporary cardiac pacing appears to be very effective in the short-term management of
these patients. Use of type I antiarrhythmic agents in patients with drug-induced PVT generally resulted
in aggravation of arrhythmia. In contrast, long-term amiodarone therapy for control of the original
arrhythmia appears to be a promising approach for those with PVT associated with type I agents.
Circulation 74, No. 2, 340-349, 1986.
THE CLINICAL characterization of polymorphous
ventricular tachycardia (PVT) has been incomplete.
The definition of PVT we have used is similar to that
proposed by the North American Society of Pacing and
Electrophysiology, namely ventricular tachycardia
with an unstable (continuously varying) QRS complex
morphology in any recorded electrocardiographic
lead.' In addition, we require a ventricular rate greater
than 200/min for at least 10 complexes. This definition
includes but is not limited to the classic torsade de
pointes pattern.2 Diagnostic criteria for torsade de
pointes includes the presence of a prolonged QT interval, and others have emphasized the clinical importance of this arrhythmia. `
Since the clinical implication of PVT is not clear,
the purpose of the present study is threefold: (1) to
define the clinical characteristics of PVT, (2) to assess
the efficacy of available emergent and long-term therapy for this arrhythmia, and (3) to examine the imporFrom the Department of Medicine and the Cardiovascular Research
Institute, University of California, San Francisco.
Address for correspondence: Melvin M. Scheinman, M.D., Room
312 Moffitt Hospital, University of California, San Francisco, CA
94143-0214.
Received Oct. 29, 1985; revision accepted April 24, 1986.
340
tance of the QT interval in patients with this arrhyth-
mia.
Materials and methods
Data for this study were collected retrospectively for 1 year
and prospectively over 1.8 years for all patients admitted to the
University of California Medical Center, San Francisco, with
the diagnosis of PVT. PVT was defined as a rapid (> 200/min)
irregular ventricular tachycardia with continuous variation in
QRS complexes of greater than 10 beat duration. This definition
included but was not limited to the classic torsade de pointes
pattern. All rhythm strips were reviewed to ascertain that the
tachycardia fulfilled the above requirements. All patients had
symptomatic arrhythmias and were continuously monitored in a
coronary care unit. PVT was defined as drug induced if it
developed as a new rhythm disturbance after initiation of drug
therapy and it disappeared after cessation of administration of
that drug. A total of 45 patients met these criteria and were
included in the study. We excluded all patients who developed
PVT as part of a preterminal cardiac state (i.e., those with
severe end-stage heart failure or cardiogenic shock). In addition, patients with familial or idiopathic long QT syndrome
were excluded, since these patients are described in detail in a
separate report.8 Patients were included only if 12-lead sinus
rhythm electrocardiograms had been recorded in them either
just before or during interludes between bouts of PVT. Posttreatment QT intervals were not measured in seven patients who
received permanent pacemakers.
The following data were extracted from the medical records:
age, sex, cardiac diagnosis, concurrent drug therapy, and drug
CIRCULATION
THERAPY AND PREVENTION-VENTRICULAR TACHYCARDIA
to be absent at follow-up after hospital discharge. A treatment
and electrolyte levels. The QT interval and the corrected QT
(QTc) were determined from a 12-lead sinus rhythm electrocardiogram that was obtained on hospital admission, during interludes between episodes of active arrhythmia, and just before
discharge. Retrospective data were obtained by examination of
all medical records, including daily electrocardiographic
rhythm strips. There was no significant difference in the incidence of PVT in retrospective vs prospectively entered patients.
The QT interval was measured according to the method suggested by Lepeshkin9 and the QT was corrected for heart rate: QTc
= QT/VRR. Short- and long-term therapy was noted and follow-up information was obtained either during visits to our
arrhythmia clinic or from private physicians.
-
regiinen was deemed unsuccessful if PVT frequency remained
the same or increased or if PVT recurred more than four drug
half-lives after discontinuing an offending drug. The total number of episodes of PVT during short-term therapy was recorded
(see table 2).
Results
The clinical data
on
the 45 patients
are
recorded in
tables 1 to 3. There were 22 female and 23 male patients ranging in age from 15 to 82 years. The majority
had organic cardiac disease, most frequently coronary
A treatment regimen for PVT was judged successful if there
artery disease and/or hypertension. Coexistent cardiac
diseases without metabolic or drug-related abnormal-
was complete cessation of the arrhythmia and was considered
possibly successful if the arrhythmia decreased in frequency
consistent with the drug half-life. In addition, for treatment to
be considered successful PVT or symptomatic arrhythmias had
ity included ischemic heart disease in three, cardio-
TABLE 1
Drug-induced PVT
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Before
Active
Patient Age (yr)/
Sex
No.
level
Drug
(,ugg/ml)
discharge
arrhythmia
Time
K+ level
elapsedA
(meq/1)B
QT
QTc
QT
QTc
years
days
days
weeks
days
day
days
weeks
years
days
years
days
days
weeks
weeks
days
months
days
2 days
3 days
3.7
4.5
3.7
3.9
4.0
3.2
4.0
4.6
4.3
4.2
3.7
0.58
Pacedc
0.56
0.46
0.48
0.56
0.44
0.44
0.40
0.56
0.50
0.44
0.48
0.56
0.68
0.40
0.50
Paced
0.36
0.48
0.46
0.52
0.38
0.48
0.44
0.40
0.48
0.56
0.44
0.38
0.50
0.40
0.46
0.52
0.40
0.40
0.48
0.40
0.40
0.44
0.42
Original
arrhythmia
Type I drug
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
53/F
74/F
50/F
60/F
68/M
59/M
65/F
77/M
66/M
82/F
70/F
60/F
73/M
81/F
70/M
65/M
15/M
67/M
63/F
70/F
70/M
69/M
79/M
Disopyramide
Procainamide
Quinidine
Quinidine
Quinidine
Procainamide
Procainamide
Quinidine
Quinidine
Quinidine
Procainamide
Quinidine
Quinidine
Quinidine
Quinidine
Quinidine
Quinidine
Procainamide
Quinidine
Procainamide
Procainamide
Quinidine
Quinidine
Sotalol
60/F
24D
Amiodarone induced
Amiodarone
73/M
25
1.3
3.4
3.8
6.4
11.1
4.9
2.1
1.9
2.9
4.2
5.4
1.2
11.3
4.2
3.8
3.4
-
SVT
PVC
PVC
A fib
SVT
SVT
PVC
SVT
PVC
PVC
SVT
A fib
SVT
A fib
SVT
A fib
A fib
SVT
PVC
PVC
A fib
USVT
A fib
USVT
1.5
3
8
1.5
2
1
4
2.2
1.5
8
2
2
7
2.5
3
9
3
3
2.5
0.48
5
2
days
days
days
days
3.2
3.6
4.0
4.0
4.3
0.48
0.62
0.40
0.34
0.52
0.53
0.56
0.50
0.44
0.50
0.58
0.54
0.48
0.52
0.53
0.66
0.42
0.44
0.44
0.42
0.50
0.58
0.48
0.53
0.42
0.40
0.50
SVT
3
months
2.4
0.66
0.70
0.42
USVT
USVT
1
day
days
3.8
0.48
0.52
2
4.1
0.52
0.60
Paced
PacedC
4
3
4.0
5.1
4.6
4.2
4.4
0.40
0.40
0.42
0.48
0.40
0.45
0.50
0.48
0.50
0.50
0.48
0.46
0.54
0.47
0.50
0.44
0.50
0.42
0.52
0.52
0.46
0.48
0.45
0.44
0.52
0.47
hypokalemia
26
27
61/F
68/M
Amiodarone
Amiodarone
A fib = atrial fibrillation; PVC = premature ventricular complex; SVT = sustained ventricular tachycardia; USVT
tachycardia.
ATime from initiation of drug to onset of PVT.
BAt the time of arrhythmia.
CPerlmanent pacing.
DSotalol in addition has both /3-blocker and class 1II antiarrhythmic action.
Vol. 74, No. 2, August 1986
unsustamied vcntnicular
341
NGUYEN et al.
myopathy in three, and mitral valve prolapse in two.
PVT was induced by exercise in four and associated
with bradyarrhythmia in two patients.
Drug-induced
PVT. Drug-induced
PVT
was
associat-
ed with quinidine in 15 patients, procainamide in seven, disopyramide and sotalol in one each, and amio-
darone in three (table 1). These drugs were originally
used to treat symptomatic unimorphic ventricular tachycardia in 13 patients, frequent premature ventricular
depolarizations in seven, and atrial fibrillation in seven. In three of the 27 patients (Nos. 7, 19, and 20),
associated mild hypokalemia was found at the time of
TABLE 2
Treatment and follow-up of patients with drug-induced PVT
Patient
No.
Baseline
incidence
of druginduced
PVT l Initial treatmentA
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1
2
2
2
Lidocaine
Disopyramide
3
4
2
5
6
Lidocaine
Lidocaine
Procainamide
6
7
4
2
8
11
9
4
10
1
11
12
13
2
2
8
14
2
15
5
16
17
18
2
6
1
2
19
20
1
21
22
23
24
25
1
1
2
3
2
26
4
3
27
d/c
1
=
Lidocaine
Lidocaine,
bretylium
Phenytoin, lidocaine
Short-term therapy
PVT
2
2
Paced
d/c disopyramide;
lidocaine
3
2
4
34
8
Lidocaine,
procainamide
Lidocaine
1
2
2
0
6
7
2
2
2
28
25
d/c procainamide;
lidocaine
0
None
None
Amiodarone
30
41
16
amiodarone
0
Outcome
d/c bretylium; paced
0
Amiodarone
Amiodarone
26
24
Paced
0
Procainamide
41
0
None
37
0
None
36
0
Amiodarone
Disopyramide
Amiodarone
39
26
0
No drugs
6
Sudden death
Amiodarone
7
Death due to pulmonary
toxicity
iv
d/c procainamide;
lidocaine
d/c procainamide;
paced
Paced
Disopyramide
d/c procainamide; paced
0
0
d/c procainamide;
paced
Tocainide
Paced
Paced
Died suddenly
0
Digoxin, verapamil
Propranolol
Amiodarone
13
10
7
0
No drugs
No drugs
12
6
Amiodarone
Amiodarone
Amiodarone
Amiodarone
Phenytoin
2
3
4
3
25
Phenytoin
Phenytoin
26
18
0
0
Procainamide d/c because
of side effects after 6
months
1
0
2
d/c bretylium and
phenytoin; paced
0
12
4
Lidocaine
0
0
2
5
1
2
7
d/c bretylium; paced,
start phenytoin
0
phenytoin,
paced
Phenytoin, paced
Died of congestive heart
failure
0
1
0
discontinued.
Alnitial therapy included discontinuation of the offending drug listed in table
342
Follow-up
(months)
Nadolol
None
0
0
therapy
0
0
0
2
Lidocaine
Lidocaine
Lidocaine,
start sotalol
Lidocaine
Start bretylium,
phenytoin
Paced
Procainamide
Start procainamide
Lidocaine
Lidocaine,
bretylium,
paced
Lidocaine,
procainamide
Quinidine
PVT 1
0
Procainamide
Lidocaine,
procainamide
Lidocaine,
procainamide
Lidocaine
Subsequent therapy
Long-term
antiarrhythmic
1.
CIRCULATION
THERAPY AND PREVENTION-VENTRICULAR TACHYCARDIA
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PVT. All patients with drug-induced PVT had associated organic heart disease. All but one of the recorded
instances of drug-induced PVT showed a long-short
initiating sequence (figures 1 and 2). The time between
initiation of therapy and the first documented episode
of PVT was from 12 hr to 4 days in 12 and from 5 days
to 2 weeks in seven. Eight patients developed PVT 2
weeks or more after initiation of drug therapy and
possible aggravating factors resulting in induction of
PVT included development of hypokalemia in two and
bradycardia in one. One of the eight patients had double-outlet right ventricle and PVT developed after tricuspid valve replacement. The latter patient had been
successfully treated with quinidine for atrial fibrillation for 4 years, but developed cardiac arrest due to
recurrent PVT when quinidine was reinitiated for treatment of atrial fibrillation 3 months after successful
cardiac surgery. No other drug was used, nor was an
electrolyte abnormality detected at the time of PVT.
Short-term therapy of drug-induced PVT. The results
of short-term therapy for control of drug-induced PVT
detailed in table 2. Repeated intravenous bolus (50
are
to 100 mg) infusions of lidocaine followed by infusions of 2 to 3 mg/min were initiated in 21 patients.
Cessation of administration of the offending drug and
the use of lidocaine resulted in complete suppression of
PVT in nine and possible suppression of PVT in three
patients (Nos. 6, 17, 26) and was ineffective in 12
patients. Temporary atrial (four patients) or ventricular
pacing (nine patients) was initiated for those suffering
hemodynamically unstable episodes of PVT. The rate
of pacing was initially adjusted (90 to 1 10/min) to
control episodes of PVT and it was gradually decreased over a 3 day observation period. Temporary
cardiac pacing proved completely effective in 11 patients (figure 1; table 2), while two patients (Nos. 25,
26) experienced breakthrough PVT when the rate of
pacing was decreased but responded to an increased
rate. The patients responded to cardiac pacing regardless of whether the baseline QT interval was normal or
prolonged. Intravenous bretylium was used in three
and was associated with increased frequency of PVT
TABLE 3
Patients with miscellaneous causes of PVT
K+ level
Patient Age (yr)/
Sex
No.
Organic heart disease
Metabolic-electrolyte
34/M Alcoholic cardiomyopathy
28
68/M None
29
30
59/M None
63/F None
31
Exercise-induced
34/M None
32
15/F Ebstein's anomaly
33
34
53/M Arrhythmogenic RV dysplasia
42/M None
35
Ischemic heart disease
61/M CAD
36
50/M CAD
37
58/M CAD
38
Bradyarrhythmia
51/F Hypertension
39
59/F
40
MVP and myocardiopathy
41
69/F Cardiomyopathy
74/F CHF, COPD
42
71/F CHF, COPD
43
44
25/F MVP
32/F MVP
45
Active
Before
arrhythmia
discharge
Failed
(meq/l)A
QT
QTc
QT
QTc
2.6
2.6
Mg++ = 1.1
Ca++=7.9
3.0
0.40
0.36
0.46
0.43
0.36
0.48
0.46
0.45 P, Pr
0.56
0.60
0.52
0.58
0.48
0.46
0.56 Q, P, B
0.44
K+ replacement
K' and Mg++ replacement
Ca++ replacement
K+ replacement
4.5
4.1
4.3
4.3
0.34
0.42
0.44
0.39
0.40
0.44
0.48
0.39
0.44
0.60
0.44
0.44
0.40
0.54
0.40
0.38
Nadolol
Nadolol + verapamil
Nadolol
Atenolol
-
0.40
0.36
0.38
0.46
0.42
0.40
0.44
0.36
0.44
0.49 Q, P, B
0.46 P
0.46 P, B
Amiodarone, phenytoin
0.44
0.44
0.52
0.49
Paced
Paced
P, D, B
0.36
PacedB
0.36
0.40
0.50
0.46
0.42
Paced
PacedB
0.36
0.48
4.2
3.8
3.5
3.8
4.1
4.0
3.3
0.40
0.40
0.55
treatment Long-term treatment
Amiodarone
Amiodarone
Pennanent pacing
0.42
Ph. Q, P
Q, P
0.42
0.55 D, P, T
Permanent pacing
Amiodarone, AICD
No drugs
Paced at 85 bpm
Atenolol
Nadolol
B = bretylium; CAD = coronary artery disease; CHF = congestive heart failure; COPD chronic obstruction lung disease; D = disopyramide;
MVP = mitral valve prolapse; Ph = phenytoin; Pr = propranolol; Q = quinidine; RV - right ventricular; T = tenormin.
AAt the time of arrhythmia.
"Permanent pacing.
Vol. 74, No. 2,
August 1986
343
NGUYEN et al.
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FIGURE 1. Electrocardiographic strips from a patient (No. 18) with procainamide-induced PVT. Top, PVT is initiated after a
long-short sequence. Middle, PVT was terminated by a direct-current external shock. The rhythm stabilized after initiation of
ventricular pacing at 100 beats/min (bottom).
whether used singly (patients 7 and 25) or with phenytoin (patient 20).
Therapy with class IA antiarrhythmic agents was
initiated 18 to 48 hr after the last recorded episode of
PVT in 12 patients. PVT either recurred or increased in
frequency in 10. Two patients (Nos. 8 and 12) developed PVT in association with quinidine but responded
to procainamide (one patient) and disopyramide (one
patient). Both the QT and QTc for these two patients
were clearly prolonged. One patient (No. 6) received a
bolus infusion of intravenous amiodarone (5 mg/kg)
followed by an infusion of 1 g over 24 hr, which
resulted in PVT control. None of these patients received intravenous Mg + or isoproterenol.
Among the three patients who developed PVT while
taking amiodarone, associated hypokalemia was found
in one and bradyarrhythmias were found in two. The
patients were treated with phenytoin (three patients),
K' replacement (one patient), or long-term cardiac
pacing (two patients).
Long-term antiarrhythmic treatment. Long-term antiarrhythmic therapy was discontinued in eight patients
because the original indication for its use was marginal. Seven patients were treated with digitalis, verap-
FIGURE 2. Patient (No. 15) with quinidine-induced PVT shows an unusual pattern of arrhythmia initiation for patients with
drug-induced PVT in that no preceding long-short sequence was recorded.
344
CIRCULATION
THERAPY AND PREVENTION-VENTRICULAR TACHYCARDIA
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amil, 13-blockers, or phenytoin for control of symptomatic premature ventricular complexes or for rate
control (for those with atrial fibrillation). Long-term
therapy with amiodarone was used for control of the
original arrhythmia in 12 patients. Two patients (Nos.
8 and 12) were. treated over the long term with procainamide and disopyramide for control of ventricular
tachycardia and paroxysmal atrial fibrillation, respectively.
QT interval. The QT and QTc recorded from at least
two 12-lead electrocardiograms between episodes of
PVT ranged from 0.40 to 0.68 and 0.42 to 0.66 sec,
respectively. The QT exceeded 0.48 sec in 10 of the 27
patients. There was no significant change in either the
QT (0.40 + 0.08 sec) or QTc (0.50 + 0.60 sec)
measured before or between interludes of PVT compared with those recorded (0.45 + 0.05 and 0.48 +
0.30 sec) in patients on long-term therapy. The QT
interval between episodes of PVT ranged from 0.40 to
0.48 sec in eight of the 13 patients who underwent
cardiac pacing, while the QTc ranged from 0.40 to
0.48 sec in four of the 13. Of note is the fact that 12
patients who developed drug-induced PVT responded
to long-term amiodarone therapy, often in spite of further prolongation of the QT interval.
Follow-up data. The follow-up data are recorded in
table 2. Four patients died during a mean follow-up
interval of 19 13 months. Two patients treated with
amiodarone died: one (No. 11) died suddenly 1 month
after hospital discharge and one (No. 15) died of amiodarone pulmonary toxicity 7 months after discharge.
One patient (No. 14) who was not receiving antiarrhythmic drugs died suddenly 6 months after hospital
discharge. One patient (No. 25) died of congestive
heart failure 25 months after discharge. The remaining
patients are alive and free of symptomatic arrhythmias.
Repeated 24 hr ambulatory electrocardiographic recordings were available for all patients treated with
long-term amiodarone therapy and for seven of the
remaining patients with drug-induced PVT. None of
these follow-up recordings showed PVT.
tinued. Only one other patient in this category had a
prolonged QT interval, and this interval remained prolonged even after Ca+ + repletion. In all four patients,
PVT responded to correction of the abnormality.
Exercise-induced PVT Four patients had PVT that was
associated with exercise: two had no organic heart
disease, another had Ebstein's anomaly associated
with mitral and tricuspid prolapse, and a third had
arrhythmogenic right ventricular dysplasia. The control QT interval was normal for each patient, but became abnormally prolonged in one after therapy with
,3-blockers. All of these patients responded to /3blockers alone or in combination with verapamil.
Acute myocardial infarction - cardiomyopathy. Three
patients developed PVT after acute myocardial infarction (Nos. 36, 37, and 38) and all showed a variable
spontaneous cycle length preceding initiation of PVT
(figure 3). These patients were treated with nitrates, /blockers, and type I drugs, but all required amiodarone
for arrhythmia control. Two patients with bradycardiarelated PVT responded to penranent cardiac pacing
and two patients with severe congestive heart failure
and chronic lung disease responded to treatment of the
underlying condition. One patient with cardiomyopathy had a history of recurrent syncope and documented cardiac arrest (PVT degenerating to ventricular fibrillation). Twenty four-hour Holter recordings
showed recurrent episodes of PVT. She was treated
with amiodarone and an automatic implantable cardioverter defibrillator (AICD) was implanted. Over a follow-up period of 12 months, she has been without
syncope and without discharge of her AICD. Prior
drug trials with type LA antiarrhythmic agents for patients in the miscellaneous cause category (table 3)
proved either ineffective or resulted in aggravation of
the arrhythmia. This occurred whether the QT interval
was normal or prolonged. Over a follow-up interval of
18 + 9 months in the miscellaneous cause group, two
patients (Nos. 42, 43) died of congestive heart failure.
Patients treated with amiodarone or ,8-blockers remain
arrhythmia free.
Miscellaneous causes of PVT
Electrolyte abnormalities. In four patients, PVT was
associated with abnormal low levels of serum K',
Mg+ +, or Ca + (table 3). In one patient (No. 31), the
arrhythmia was probably due to thioridazine and hypokalemia. She had been treated with thioridazine for 4
years and developed PVT only after initiation of diuretic therapy, which resulted in hypokalemia. Her QT
and QTc were prolonged at the time of PVT, but these
intervals returned to baseline values when her potassium levels were corrected and her thioridazine discon-
Discussion
Previous authors have emphasized the clinical importance of diagnosing torsade de pointes. This arrhythmia is diagnosed when the following features are
present: (1) paroxysms of ventricular tachycardia during which the rhythm is irregular with rates of 200 to
250 beats/min, (2) progressive changes in amplitude
and polarity of the QRS complexes such that the QRS
axis changes and the complexes appear to be twisting
around the isoelectric baseline, (3) spontaneous termi-
Vol. 74, No. 2,
August 1986
345
NGUYEN et al.
A~~
A .jT7
T
~
B
C
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0
FIGURE 3. Representative strips from a patient who developed PVT after acute myocardial infarction. A, Normal QT interval
(0. 30 sec) and heart rate (75 beats/min). B to D, Varying patterns of initiating sequences of PVT. PVT is initiated by progressive
cycle length shortening in B, long-short sequence in C, and during sinus rhythm at rate of 72 beats/min in D.
nation of most episodes, (4) occasional progression of
the arrhythmia to sustained unimorphic ventricular
tachycardia or ventricular fibrillation, and (5) a prolonged QT interval. In this report, we chose the more
general term PVT (as suggested by Sclarovsky et al.10)
for three reasons: (1) In many instances, it proved
impossible to be certain whether the arrhythmia
showed the characteristic pattern of twisting around
the isoelectric baseline. (2) In some instances, a typical
pattern of twisting around the baseline was associated
with a normal QT interval. (3) In others, a long QT was
associated with a polymorphous configuration that was
clearly not characterized by twisting of the QRS complexes around the isoelectric baseline.
It has been emphasized that those with classic torsade de pointes tend to respond to maneuvers that
shorten the QT (i.e., cardiac pacing or isoproterenol
infusion).3 5,6 In contrast, those with PVT and a normal QT are thought to respond to conventional type I
antiarrhythmic drugs.3 In addition, one report suggests
that those patients with drug-induced torsade de
pointes show markedly prolonged QT intervals (> 0.6
sec).6 Our data suggest that the above formulation may
not be relevant for the majority of patients presenting
346
with drug-induced PVT. We found that in the majority
of patients with PVT the tachycardia was drug induced
and that the QT interval was of limited value in deciding on proper therapy for these patients. For example,
only three patients with drug-induced PVT showed QT
prolongation of greater than 0.60 sec, suggesting that
this criterion is not applicable in the diagnosis of druginduced PVT. In addition, six patients with drug-induced PVT and normal (or slightly prolonged) QT
intervals failed to respond to other type I antiarrhythmic agents. Furthermore, temporary cardiac pacing
proved effective regardless of whether the QT was
normal or prolonged. Finally, two patients (Nos. 8 and
12) with clearly prolonged QT intervals who had quinidine-induced PVT responded to procainamide (one patient) and disopyramide (one patient). These data suggest that recognition of the PVT pattern as described
(see Materials and methods) is crucial in arriving at
proper therapy, while the absolute or corrected QT is
of limited value.
Reports by Denes et al. ` and Kay et al. 12 emphasize
the consistent finding of a pause that precedes the onset
of drug-induced torsade de pointes. Of interest was our
finding that this same pattern was almost universally
CIRCULATION
THERAPY AND PREVENTION-VENTRICULAR TACHYCARDIA
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present in those with drug-induced PVT. This finding
and the beneficial response to pacing may reflect a
pathogenetic mechanism common to both torsade de
pointes and PVT. Pause-related PVT was not a consistent finding in those with PVT unassociated with
drugs. For example, in those with PVT associated with
exercise, the arrhythmia became apparent only after a
critical increase in sinus rate was achieved.
Time elapsed from onset of drug therapy to PVT. An
important finding in our study relates to the onset of
PVT. One-half of the patients with type I drug-induced PVT (12 of 24) developed the tachycardia within 4 days of initiation of drug therapy. In eight, PVT
developed weeks to years after initiation of the offending drug. In those with late-onset PVT, associated
hypokalemia was found in two, bradycardia was noted
in one, and in another patient PVT was observed after
successful cardiac surgery for tricuspid valve replacement. As a group, these patients developed PVT while
taking their regular dosage of medication. Drug blood
levels were available for 17 patients and were found to
be in the subtherapeutic or therapeutic range in 15 of
the 17, suggesting that drug-induced PVT was an idiosyncratic response. Thus, a 4 day hospital stay for all
patients initiated on type I antiarrhythmic drug therapy
should be sufficient to detect a significant number of
patients at risk for development of PVT. Similar findings have been reported in a prospective evaluation of
quinidine therapy.'6
Miscellaneous causes of PVT. Torsade de pointes associated with electrolyte disorders, myocardial ischemia,
and bradyarrhythmias has been described in previous
reports.'7 21 Two of the four patients with electrolyte
abnormalities (Nos. 30 and 31) exhibited a prolonged
QT interval. In patient 30, the prolonged QT may have
been due to the underlying cardiomyopathy since correction of the hypocalcemia (while associated with
abatement of PVT) failed to normalize the QT interval.
In the 10 patients with ischemic heart disease or bradyarrhythmia-related PVT, the QT was either normal or
only slightly prolonged. Of particular interest are four
patients with exercise-induced PVT. None of these
patients had coronary artery disease but two had organic cardiac disease (Ebstein's anomaly in patient 33,
and arrhythmogenic right ventricular dysplasia in patient 34). The QT interval in these patients was either
normal or borderline prolonged and each responded (as
judged by repeated exercise treadmill testing) to ,3blockers alone or in combination with verapamil (patient 33). Exercise-induced "pleomorphic" ventricular
tachycardia in the absence of coronary artery disease
has been previously described.22,23
Vol. 74, No. 2, August 1986
Short-term therapy of PVT. Short-term treatment with
intravenous lidocaine was associated with inconsistent
benefit. This is in accord with the results reported by
others for therapy of torsade de pointes. 2' '3 However,
it is often unclear whether a "positive" response to
lidocaine is in fact drug related or due to other therapy
applied (i.e., discontinuation of offending drugs, correction of electrolyte abnormalities, or pacing). We
found (as has been emphasized by others with regard to
treatment of classic torsade de pointes3' 5) that cardiac
pacing was uniquely effective in the management of
these patients. The response to cardiac pacing was,
however, clearly unrelated to whether the QT was prolonged or not. We found that use of other type I antiarrhythmic agents in patients with drug-induced PVT
generally resulted in aggravation of the arrhythmia.
While this would appear to be predictable, we are
unaware of any previous reports documenting this
finding for patients with drug-induced PVT. In addition, bretylium was also associated with arrhythmia
aggravation in three patients (Nos. 7, 20, and 25).
Long-term therapy for the original arrhythmia. Longterm amiodarone was initiated for control of the original arrhythmia in 12 patients with type I drug-induced
PVT. Long-term follow-up of this group revealed that
the arrhythmia was controlled in all, but one patient
died suddenly 1 month after discharge from the hospital. While our findings suggest that long-term therapy
with amiodarone is not proarrhythmic in those with
type I drug-induced PVT, it should be emphasized that
amiodarone itself may cause PVT.'4 The exact incidence of PVT due to amiodarone is not known, but
appears to be very low. In our total series of 460
patients treated with amiodarone, only three instances
(0.7%) of PVT were recorded. It should be emphasized that the 0.7% incidence of PVT is a minimal
figure. The overall incidence of sudden death in our
experience for patients with malignant ventricular arrhythmias treated with amiodarone is 8%,'5 and the
type of arrhythmia responsible for the sudden demise is
not known.
QT interval and PVT. The role of the QT interval in
patients with PVT remains uncertain for several reasons. First, precise measurement of the QT interval
(even from 12-lead electrocardiographic tracings) will
at times be difficult and the precise upper limits of
normal and the suggested corrections of the QT interval for rate are controversial.24 In patients with druginduced PVT, the issue is further compounded by the
inherent QT interval-lengthening effects of class I or
psychotropic agents. In our own report, for example,
the QT intervals for the bulk of patients with drug347
NGUYEN et al.
OT duration
A
0,70 -
0,65
0,60
0
Cj 0,55
0,50
0
0
0,45
0,40
U03:
-
0,50 0,60 0,70 0,80 0,90 1;00 1,10
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R-R INTERVAL
1,20
sec
FIGURE 4. The effects of quinidine on the QT interval in 20 patients
treated with this drug. The QT interval in seconds is displayed on the
ordinate while the spontaneous sinus cycle length is shown on the
abscissa. The QT interval varied from 0.35 to 0.62 sec. Four patients
who developed ventricular arrhythmias are represented by ringed circles. Note that the QT interval proved to be an insensitive guide for
predicting development of PVT. In addition, in the group of patients
who did not develop ventricular arrhythmias, the QT interval fell between 0.40 to 0.48 sec. These data were kindly provided by Drs.
Orinius and Ejvinsson.
induced PVT fell into the range expected for those
treated with type I agents but who never experienced
PVT* (figure 4). For this reason, in our study, those
patients with drug-induced PVT were not considered
to have a clearly prolonged QT interval unless this
interval exceeded 0.48 sec. Moreover, our data suggest that the QT interval cannot be used as a reliable
guide for deciding on short- or long-term antiarrhythmic therapy in patients with PVT because (1) most
patients with drug-induced PVT and a normal QT
failed to respond to other type I drugs, (2) cardiac
pacing was almost universally effective regardless of
the QT interval, and (3) long-term therapy with amiodarone proved effective in patients with type I drug-induced PVT and this therapy was usually associated
with further lengthening of the QT interval.
Clinical implications. The most important finding of
our study was that PVT, whether associated with normal or slightly prolonged QT intervals, was usually
drug induced. Drug-induced PVT was almost always
preceded by sinus bradycardia or a pause, while this
*Orinius E: Personal communication.
348
finding was much less consistent in those with PVT
that was not drug related. We suspect that some of the
patients with drug-induced PVT were treated with other type I agents, in part because either the QT interval
was normal or the characteristic pattern of twisting of
the QRS around an isoelectric line was not present. We
therefore believe that the critical element in the proper
management of these patients is recognition of the
PVT pattern. Intravenous lidocaine was inconsistently
effective. Intravenous bretylium was ineffective and
probably proarrhythmic, while cardiac pacing was almost universally effective in arrhythmia control, regardless of the QT interval. A 4 day hospital stay
would be expected to detect approximately half of patients susceptible to type I drug-induced PVT. In addition, other possible aggravating causes, such as occurrence of bradyarrhythmia, electrolyte disorders, use of
diuretic agents, or cardiac surgery should be evaluated. Our preliminary findings suggest that amiodarone
may prove to be a suitable therapeutic option for longterm control of the original arrhythmia in patients with
drug-induced PVT.
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349
Polymorphous ventricular tachycardia: clinical characterization, therapy, and the QT
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P T Nguyen, M M Scheinman and J Seger
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Circulation. 1986;74:340-349
doi: 10.1161/01.CIR.74.2.340
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