polymorphous ventricular characterization, therapy,...

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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. 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 inter- val, and others have emphasized the clinical impor- tance 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 ther- apy for this arrhythmia, and (3) to examine the impor- From 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. 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 addi- tion, 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. Post- treatment 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 340 by guest on July 7, 2018 http://circ.ahajournals.org/ Downloaded from

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THERAPY AND PREVENTIONVENTRICULAR TACHYCARDIA

Polymorphous ventricular tachycardia: clinicalcharacterization, therapy, and the QT intervalPHuC TITo NGUYEN, B.S., MELVIN M. SCHEINMAN, M.D., AND JOHN SEGER, M.D.

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 infour patients. Coexistent cardiac diseases without metabolic or drug-related abnormalities includedischemic heart disease in three, cardiomyopathy in three, and mitral valve prolapse in two. PVT wasexercise-induced in four and associated with bradyarrhythmias in two. A prolonged QT or correctedQT interval was inconsistently related to the occurrence of PVT. In patients in whom PVT was inducedby certain type I drugs, other type I antiarrhythmic drugs were usually either ineffective or resulted inaggravation of arrhythmia. For the group as a whole, treatment with lidocaine resulted in inconsistentbeneficial effects, while cardiac pacing was almost universally effective for those with drug-inducedPVT, regardless of the length of the QT interval. Long-term amiodarone therapy proved safe andeffective for 12 of the 24 patients with drug-induced PVT who required long-term therapy for theiroriginal arrhythmia. We conclude that identification of PVT is the key clinical issue and that the QTinterval is not necessarily the prime abnormality nor the variable to be considered in predicting successof therapy. Temporary cardiac pacing appears to be very effective in the short-term management ofthese patients. Use of type I antiarrhythmic agents in patients with drug-induced PVT generally resultedin aggravation of arrhythmia. In contrast, long-term amiodarone therapy for control of the originalarrhythmia 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 polymorphousventricular tachycardia (PVT) has been incomplete.The definition of PVT we have used is similar to thatproposed by the North American Society of Pacing andElectrophysiology, namely ventricular tachycardiawith an unstable (continuously varying) QRS complexmorphology in any recorded electrocardiographiclead.' In addition, we require a ventricular rate greaterthan 200/min for at least 10 complexes. This definitionincludes but is not limited to the classic torsade depointes pattern.2 Diagnostic criteria for torsade depointes includes the presence of a prolonged QT inter-val, and others have emphasized the clinical impor-tance of this arrhythmia. `

Since the clinical implication of PVT is not clear,the purpose of the present study is threefold: (1) todefine the clinical characteristics of PVT, (2) to assessthe efficacy of available emergent and long-term ther-apy for this arrhythmia, and (3) to examine the impor-

From the Department of Medicine and the Cardiovascular ResearchInstitute, University of California, San Francisco.

Address for correspondence: Melvin M. Scheinman, M.D., Room312 Moffitt Hospital, University of California, San Francisco, CA94143-0214.

Received Oct. 29, 1985; revision accepted April 24, 1986.

tance of the QT interval in patients with this arrhyth-mia.

Materials and methodsData for this study were collected retrospectively for 1 year

and prospectively over 1.8 years for all patients admitted to theUniversity of California Medical Center, San Francisco, withthe diagnosis of PVT. PVT was defined as a rapid (> 200/min)irregular ventricular tachycardia with continuous variation inQRS complexes of greater than 10 beat duration. This definitionincluded but was not limited to the classic torsade de pointespattern. All rhythm strips were reviewed to ascertain that thetachycardia fulfilled the above requirements. All patients hadsymptomatic arrhythmias and were continuously monitored in acoronary care unit. PVT was defined as drug induced if itdeveloped as a new rhythm disturbance after initiation of drugtherapy and it disappeared after cessation of administration ofthat drug. A total of 45 patients met these criteria and wereincluded in the study. We excluded all patients who developedPVT as part of a preterminal cardiac state (i.e., those withsevere end-stage heart failure or cardiogenic shock). In addi-tion, patients with familial or idiopathic long QT syndromewere excluded, since these patients are described in detail in aseparate report.8 Patients were included only if 12-lead sinusrhythm electrocardiograms had been recorded in them eitherjust before or during interludes between bouts of PVT. Post-treatment QT intervals were not measured in seven patients whoreceived permanent pacemakers.The following data were extracted from the medical records:

age, sex, cardiac diagnosis, concurrent drug therapy, and drug

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and electrolyte levels. The QT interval and the corrected QT to be absent at follow-up after hospital discharge. A treatment(QTc) were determined from a 12-lead sinus rhythm electrocar- regiinen was deemed unsuccessful if PVT frequency remaineddiogram that was obtained on hospital admission, during inter- the same or increased or if PVT recurred more than four drugludes between episodes of active arrhythmia, and just before half-lives after discontinuing an offending drug. The total num-discharge. Retrospective data were obtained by examination of ber of episodes of PVT during short-term therapy was recordedall medical records, including daily electrocardiographic (see table 2).rhythm strips. There was no significant difference in the inci-dence of PVT in retrospective vs prospectively entered patients. ResultsThe QT interval was measured according to the method suggest-ed by Lepeshkin9 and the QT was corrected for heart rate: QTc The clinical data on the 45 patients are recorded in= QT/VRR. Short- and long-term therapy was noted and fol- tables 1 to 3. There were 22 female and 23 male pa-low-up information was obtained either during visits to our tients ranging in age from 15 to 82 years. The majorityarrhythmia clinic or from private physicians. --A treatment regimen for PVT was judged successful if there had organic cardiac disease, most frequently coronary

was complete cessation of the arrhythmia and was considered artery disease and/or hypertension. Coexistent cardiacpossibly successful if the arrhythmia decreased in frequency diseases without metabolic or drug-related abnormal-consistent with the drug half-life. In addition, for treatment tobe considered successful PVT or symptomatic arrhythmias had ity included ischemic heart disease in three, cardio-

TABLE 1Drug-induced PVT

Active Before

Patient Age (yr)/ level Original Time K+ level arrhythmia discharge

No. Sex Drug (,ugg/ml) arrhythmia elapsedA (meq/1)B QT QTc QT QTc

Type I drug1 53/F Disopyramide 1.3 SVT 1.5 years 3.7 0.58 0.56 0.50 0.46

2 74/F Procainamide 3.4 PVC 3 days 4.5 Pacedc Paced

3 50/F Quinidine - PVC 8 days - 0.48 0.53 0.36 0.40

4 60/F Quinidine 3.8 A fib 1.5 weeks 3.7 0.56 0.56 0.48 0.45

5 68/M Quinidine 6.4 SVT 2 days 3.9 0.44 0.50 0.46 0.50

6 59/M Procainamide - SVT 1 day 4.0 0.44 0.44 0.52 0.48

7 65/F Procainamide 11.1 PVC 4 days 3.2 0.40 0.50 0.38 0.50

8 77/M Quinidine 4.9 SVT 2.2 weeks 4.0 0.56 0.58 0.48 0.50

9 66/M Quinidine 2.1 PVC 1.5 years 4.6 0.50 0.54 0.44 0.48

10 82/F Quinidine 1.9 PVC 8 days 4.3 0.44 0.48 0.40 0.46

11 70/F Procainamide - SVT 2 years 4.2 0.48 0.52 0.48 0.54

12 60/F Quinidine 2.9 A fib 2 days 3.7 0.56 0.53 0.56 0.47

13 73/M Quinidine - SVT 7 days 0.68 0.66 0.44 0.50

14 81/F Quinidine 4.2 A fib 2.5 weeks 4.0 0.40 0.42 0.38 0.44

15 70/M Quinidine 5.4 SVT 3 weeks 5.1 0.40 0.44 0.50 0.50

16 65/M Quinidine 1.2 A fib 9 days 4.6 0.40 0.44 0.40 0.42

17 15/M Quinidine A fib 3 months 4.2 0.42 0.42 0.46 0.52

18 67/M Procainamide 11.3 SVT 3 days 4.4 0.48 0.50 0.52 0.52

19 63/F Quinidine 4.2 PVC 2 days 2.5 0.48 0.58 0.40 0.46

20 70/F Procainamide 3.8 PVC 3 days 3.2 0.48 0.48 0.40 0.48

21 70/M Procainamide - A fib 4 days 3.6 0.62 0.53 0.48 0.45

22 69/M Quinidine 3.4 USVT 3 days 4.0 0.40 0.42 0.40 0.44

23 79/M Quinidine - A fib 5 days 4.0 0.34 0.40 0.40 0.52

24D 60/F Sotalol USVT 2 days 4.3 0.52 0.50 0.44 0.47

Amiodarone induced25 73/M Amiodarone SVT 3 months 2.4 0.66 0.70 0.42 0.42

hypokalemia26 61/F Amiodarone USVT 1 day 3.8 0.48 0.52 Paced

27 68/M Amiodarone USVT 2 days 4.1 0.52 0.60 PacedC

A fib = atrial fibrillation; PVC = premature ventricular complex; SVT = sustained ventricular tachycardia; USVT unsustamied vcntniculartachycardia.

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.

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myopathy in three, and mitral valve prolapse in two.PVT was induced by exercise in four and associatedwith bradyarrhythmia in two patients.

Drug-induced PVT. Drug-induced PVT was associat-

ed with quinidine in 15 patients, procainamide in sev-

en, disopyramide and sotalol in one each, and amio-

darone in three (table 1). These drugs were originallyused to treat symptomatic unimorphic ventricular tach-ycardia in 13 patients, frequent premature ventriculardepolarizations in seven, and atrial fibrillation in sev-

en. In three of the 27 patients (Nos. 7, 19, and 20),associated mild hypokalemia was found at the time of

TABLE 2Treatment and follow-up of patients with drug-induced PVT

Baselineincidenceof drug- Short-term therapy Long-term

Patient induced antiarrhythmic Follow-upNo. PVT l Initial treatmentA PVT Subsequent therapy PVT 1 therapy (months) Outcome

1 22 2

LidocaineDisopyramide

22

Pacedd/c disopyramide;

lidocaine

0

0

NadololNone

2825

345

22

6

LidocaineLidocaineProcainamide

0

0

3

6 4 Lidocaine7 2 Lidocaine,

bretylium8 11 Phenytoin, lidocaine

9 4 Procainamide

10 1 Lidocaine,procainamide

11 2 Lidocaine12 213 8 Lidocaine,

procainamide14 2 Lidocaine,

procainamide15 5 Lidocaine

16 2 Lidocaine17 6 Lidocaine18 1 Lidocaine,

start sotalol19 1 Lidocaine20 1 Start bretylium,

phenytoin21 1 Paced22 1 Procainamide23 2 Start procainamide24 3 Lidocaine25 2 Lidocaine,

bretylium,paced

26 4 Lidocaine,procainamide

27 3 Quinidine

24

348

d/c procainamide;lidocaine

iv amiodarone

d/c bretylium; paced

Paced

2 d/c procainamide;lidocaine

1 d/c procainamide;2 paced2 Paced0 Disopyramide6 d/c procainamide; paced7220

0

2

10

2

0

1240

25

127

d/c procainamide;paced

TocainidePacedPaced

NoneNone

0 Amiodarone

0

0

AmiodaroneAmiodarone

0 Procainamide

0 None

0 None

0

0

0

AmiodaroneDisopyramideAmiodarone

0 No drugs

Amiodarone

0

0

0

d/c bretylium andphenytoin; paced

Lidocaine

d/c bretylium; paced,start phenytoin

phenytoin,pacedPhenytoin, paced

Digoxin, verapamilPropranololAmiodarone

No drugs0 No drugs

AmiodaroneAmiodarone

0 AmiodaroneAmiodarone

0 Phenytoin

0

10

304116

2624

41 Procainamide d/c becauseof side effects after 6months

37

36

Died suddenly3926

6 Sudden death

7 Death due to pulmonarytoxicity

13107

126

2343

25

PhenytoinPhenytoin

Died of congestive heartfailure

2618

d/c = discontinued.Alnitial therapy included discontinuation of the offending drug listed in table 1.

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PVT. All patients with drug-induced PVT had associ-ated organic heart disease. All but one of the recordedinstances of drug-induced PVT showed a long-shortinitiating sequence (figures 1 and 2). The time betweeninitiation of therapy and the first documented episodeof PVT was from 12 hr to 4 days in 12 and from 5 daysto 2 weeks in seven. Eight patients developed PVT 2weeks or more after initiation of drug therapy andpossible aggravating factors resulting in induction ofPVT included development of hypokalemia in two andbradycardia in one. One of the eight patients had dou-ble-outlet right ventricle and PVT developed after tri-cuspid valve replacement. The latter patient had beensuccessfully treated with quinidine for atrial fibrilla-tion for 4 years, but developed cardiac arrest due torecurrent PVT when quinidine was reinitiated for treat-ment of atrial fibrillation 3 months after successfulcardiac 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

are detailed in table 2. Repeated intravenous bolus (50to 100 mg) infusions of lidocaine followed by infu-sions of 2 to 3 mg/min were initiated in 21 patients.Cessation of administration of the offending drug andthe use of lidocaine resulted in complete suppression ofPVT in nine and possible suppression of PVT in threepatients (Nos. 6, 17, 26) and was ineffective in 12patients. Temporary atrial (four patients) or ventricularpacing (nine patients) was initiated for those sufferinghemodynamically unstable episodes of PVT. The rate

of pacing was initially adjusted (90 to 1 10/min) tocontrol episodes of PVT and it was gradually de-creased over a 3 day observation period. Temporarycardiac pacing proved completely effective in 11 pa-

tients (figure 1; table 2), while two patients (Nos. 25,26) experienced breakthrough PVT when the rate ofpacing was decreased but responded to an increasedrate. The patients responded to cardiac pacing regard-less of whether the baseline QT interval was normal or

prolonged. Intravenous bretylium was used in threeand was associated with increased frequency of PVT

TABLE 3Patients with miscellaneous causes of PVT

Active Before

Patient Age (yr)/ K+ level arrhythmia discharge FailedNo. Sex Organic heart disease (meq/l)A QT QTc QT QTc treatment Long-term treatment

Metabolic-electrolyte28 34/M Alcoholic cardiomyopathy 2.6 0.40 0.46 0.36 0.46 K+ replacement29 68/M None 2.6 0.36 0.43 0.48 0.45 P, Pr K' and Mg++ replace-

Mg++ = 1.1 ment30 59/M None Ca++=7.9 0.56 0.52 0.48 0.56 Q, P, B Ca++ replacement31 63/F None 3.0 0.60 0.58 0.46 0.44 K+ replacement

Exercise-induced32 34/M None 4.5 0.34 0.40 0.44 0.40 Nadolol33 15/F Ebstein's anomaly 4.1 0.42 0.44 0.60 0.54 Nadolol + verapamil34 53/M Arrhythmogenic RV dysplasia 4.3 0.44 0.48 0.44 0.40 Nadolol35 42/M None 4.3 0.39 0.39 0.44 0.38 Atenolol

Ischemic heart disease36 61/M CAD - 0.40 0.46 0.44 0.49 Q, P, B Amiodarone, phenytoin37 50/M CAD 4.2 0.36 0.42 0.36 0.46 P Amiodarone38 58/M CAD 3.8 0.38 0.40 0.44 0.46 P, B Amiodarone

Bradyarrhythmia39 51/F Hypertension 3.5 0.44 0.52 Paced Pennanent pacing40 59/F 0.44 0.49 Paced P, D, B Permanent pacing

MVP and myocardiopathy41 69/F Cardiomyopathy 3.8 0.36 0.46 0.42 0.42 Amiodarone, AICD42 74/F CHF, COPD 4.1 PacedB Paced Ph. Q, P No drugs43 71/F CHF, COPD 4.0 0.36 0.40 PacedB Q, P Paced at 85 bpm44 25/F MVP 0.40 0.40 0.36 0.42 Atenolol45 32/F MVP 3.3 0.50 0.55 0.48 0.55 D, P, T 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.

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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 ofventricular pacing at 100 beats/min (bottom).

whether used singly (patients 7 and 25) or with pheny-toin (patient 20).

Therapy with class IA antiarrhythmic agents wasinitiated 18 to 48 hr after the last recorded episode ofPVT in 12 patients. PVT either recurred or increased infrequency in 10. Two patients (Nos. 8 and 12) devel-oped PVT in association with quinidine but respondedto procainamide (one patient) and disopyramide (onepatient). Both the QT and QTc for these two patientswere clearly prolonged. One patient (No. 6) received abolus 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 re-ceived intravenous Mg + or isoproterenol.Among the three patients who developed PVT while

taking amiodarone, associated hypokalemia was foundin one and bradyarrhythmias were found in two. Thepatients were treated with phenytoin (three patients),K' replacement (one patient), or long-term cardiacpacing (two patients).

Long-term antiarrhythmic treatment. Long-term an-tiarrhythmic therapy was discontinued in eight patientsbecause the original indication for its use was margin-al. 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 withdrug-induced PVT in that no preceding long-short sequence was recorded.

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amil, 13-blockers, or phenytoin for control of symp-

tomatic premature ventricular complexes or for rate

control (for those with atrial fibrillation). Long-termtherapy with amiodarone was used for control of theoriginal arrhythmia in 12 patients. Two patients (Nos.8 and 12) were. treated over the long term with procain-amide and disopyramide for control of ventriculartachycardia and paroxysmal atrial fibrillation, respec-

tively.QT interval. The QT and QTc recorded from at least

two 12-lead electrocardiograms between episodes ofPVT 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 27patients. There was no significant change in either theQT (0.40 + 0.08 sec) or QTc (0.50 + 0.60 sec)measured before or between interludes of PVT com-

pared with those recorded (0.45 + 0.05 and 0.48 +

0.30 sec) in patients on long-term therapy. The QTinterval between episodes of PVT ranged from 0.40 to

0.48 sec in eight of the 13 patients who underwentcardiac pacing, while the QTc ranged from 0.40 to

0.48 sec in four of the 13. Of note is the fact that 12patients who developed drug-induced PVT respondedto long-term amiodarone therapy, often in spite of fur-ther prolongation of the QT interval.

Follow-up data. The follow-up data are recorded intable 2. Four patients died during a mean follow-upinterval of 19 13 months. Two patients treated withamiodarone died: one (No. 11) died suddenly 1 monthafter hospital discharge and one (No. 15) died of amio-darone pulmonary toxicity 7 months after discharge.One patient (No. 14) who was not receiving antiar-rhythmic drugs died suddenly 6 months after hospitaldischarge. One patient (No. 25) died of congestiveheart failure 25 months after discharge. The remainingpatients are alive and free of symptomatic arrhythmias.Repeated 24 hr ambulatory electrocardiographic re-

cordings were available for all patients treated withlong-term amiodarone therapy and for seven of theremaining patients with drug-induced PVT. None ofthese follow-up recordings showed PVT.

Miscellaneous causes of PVTElectrolyte abnormalities. In four patients, PVT was

associated with abnormal low levels of serum K',Mg+ +, or Ca + (table 3). In one patient (No. 31), thearrhythmia was probably due to thioridazine and hypo-kalemia. She had been treated with thioridazine for 4years and developed PVT only after initiation of di-uretic therapy, which resulted in hypokalemia. Her QTand QTc were prolonged at the time of PVT, but theseintervals returned to baseline values when her potas-sium levels were corrected and her thioridazine discon-

tinued. Only one other patient in this category had aprolonged QT interval, and this interval remained pro-longed even after Ca+ + repletion. In all four patients,PVT responded to correction of the abnormality.

Exercise-induced PVT Four patients had PVT that wasassociated with exercise: two had no organic heartdisease, another had Ebstein's anomaly associatedwith mitral and tricuspid prolapse, and a third hadarrhythmogenic right ventricular dysplasia. The con-trol QT interval was normal for each patient, but be-came abnormally prolonged in one after therapy with,3-blockers. All of these patients responded to /3-blockers alone or in combination with verapamil.

Acute myocardial infarction - cardiomyopathy. Threepatients developed PVT after acute myocardial infarc-tion (Nos. 36, 37, and 38) and all showed a variablespontaneous cycle length preceding initiation of PVT(figure 3). These patients were treated with nitrates, /-blockers, and type I drugs, but all required amiodaronefor arrhythmia control. Two patients with bradycardia-related PVT responded to penranent cardiac pacingand two patients with severe congestive heart failureand chronic lung disease responded to treatment of theunderlying condition. One patient with cardiomyop-athy had a history of recurrent syncope and docu-mented cardiac arrest (PVT degenerating to ventricu-lar fibrillation). Twenty four-hour Holter recordingsshowed recurrent episodes of PVT. She was treatedwith amiodarone and an automatic implantable cardio-verter defibrillator (AICD) was implanted. Over a fol-low-up period of 12 months, she has been withoutsyncope and without discharge of her AICD. Priordrug trials with type LA antiarrhythmic agents for pa-tients in the miscellaneous cause category (table 3)proved either ineffective or resulted in aggravation ofthe arrhythmia. This occurred whether the QT intervalwas normal or prolonged. Over a follow-up interval of18 + 9 months in the miscellaneous cause group, twopatients (Nos. 42, 43) died of congestive heart failure.Patients treated with amiodarone or ,8-blockers remainarrhythmia free.

DiscussionPrevious authors have emphasized the clinical im-

portance of diagnosing torsade de pointes. This ar-rhythmia is diagnosed when the following features arepresent: (1) paroxysms of ventricular tachycardia dur-ing which the rhythm is irregular with rates of 200 to

250 beats/min, (2) progressive changes in amplitudeand polarity of the QRS complexes such that the QRSaxis changes and the complexes appear to be twistingaround the isoelectric baseline, (3) spontaneous termi-

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A.jT7 TA~~ ~

B

C

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 progressivecycle 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 ofthe arrhythmia to sustained unimorphic ventriculartachycardia or ventricular fibrillation, and (5) a pro-longed QT interval. In this report, we chose the moregeneral term PVT (as suggested by Sclarovsky et al.10)for three reasons: (1) In many instances, it provedimpossible to be certain whether the arrhythmiashowed the characteristic pattern of twisting aroundthe isoelectric baseline. (2) In some instances, a typicalpattern of twisting around the baseline was associatedwith a normal QT interval. (3) In others, a long QT wasassociated with a polymorphous configuration that wasclearly not characterized by twisting of the QRS com-plexes around the isoelectric baseline.

It has been emphasized that those with classic tor-sade de pointes tend to respond to maneuvers thatshorten the QT (i.e., cardiac pacing or isoproterenolinfusion).3 5,6 In contrast, those with PVT and a nor-mal QT are thought to respond to conventional type Iantiarrhythmic drugs.3 In addition, one report suggeststhat those patients with drug-induced torsade depointes show markedly prolonged QT intervals (> 0.6sec).6 Our data suggest that the above formulation maynot be relevant for the majority of patients presenting

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with drug-induced PVT. We found that in the majorityof patients with PVT the tachycardia was drug inducedand that the QT interval was of limited value in decid-ing on proper therapy for these patients. For example,only three patients with drug-induced PVT showed QTprolongation of greater than 0.60 sec, suggesting thatthis criterion is not applicable in the diagnosis of drug-induced PVT. In addition, six patients with drug-in-duced PVT and normal (or slightly prolonged) QTintervals failed to respond to other type I antiarrhyth-mic agents. Furthermore, temporary cardiac pacingproved effective regardless of whether the QT wasnormal or prolonged. Finally, two patients (Nos. 8 and12) with clearly prolonged QT intervals who had quini-dine-induced PVT responded to procainamide (one pa-tient) and disopyramide (one patient). These data sug-gest that recognition of the PVT pattern as described(see Materials and methods) is crucial in arriving atproper therapy, while the absolute or corrected QT isof limited value.

Reports by Denes et al. ` and Kay et al. 12 emphasizethe consistent finding of a pause that precedes the onsetof drug-induced torsade de pointes. Of interest was ourfinding that this same pattern was almost universally

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present in those with drug-induced PVT. This findingand the beneficial response to pacing may reflect apathogenetic mechanism common to both torsade depointes and PVT. Pause-related PVT was not a consis-tent finding in those with PVT unassociated withdrugs. For example, in those with PVT associated withexercise, the arrhythmia became apparent only after acritical increase in sinus rate was achieved.

Time elapsed from onset of drug therapy to PVT. Animportant finding in our study relates to the onset ofPVT. One-half of the patients with type I drug-in-duced PVT (12 of 24) developed the tachycardia with-in 4 days of initiation of drug therapy. In eight, PVTdeveloped weeks to years after initiation of the offend-ing drug. In those with late-onset PVT, associatedhypokalemia was found in two, bradycardia was notedin one, and in another patient PVT was observed aftersuccessful cardiac surgery for tricuspid valve replace-ment. As a group, these patients developed PVT whiletaking their regular dosage of medication. Drug bloodlevels were available for 17 patients and were found tobe in the subtherapeutic or therapeutic range in 15 ofthe 17, suggesting that drug-induced PVT was an idio-syncratic response. Thus, a 4 day hospital stay for allpatients initiated on type I antiarrhythmic drug therapyshould be sufficient to detect a significant number ofpatients at risk for development of PVT. Similar find-ings have been reported in a prospective evaluation ofquinidine therapy.'6

Miscellaneous causes of PVT. Torsade de pointes asso-ciated with electrolyte disorders, myocardial ischemia,and bradyarrhythmias has been described in previousreports.'7 21 Two of the four patients with electrolyteabnormalities (Nos. 30 and 31) exhibited a prolongedQT interval. In patient 30, the prolonged QT may havebeen due to the underlying cardiomyopathy since cor-rection of the hypocalcemia (while associated withabatement ofPVT) failed to normalize the QT interval.In the 10 patients with ischemic heart disease or brady-arrhythmia-related PVT, the QT was either normal oronly slightly prolonged. Of particular interest are fourpatients with exercise-induced PVT. None of thesepatients had coronary artery disease but two had organ-ic cardiac disease (Ebstein's anomaly in patient 33,and arrhythmogenic right ventricular dysplasia in pa-tient 34). The QT interval in these patients was eithernormal or borderline prolonged and each responded (asjudged by repeated exercise treadmill testing) to ,3-blockers alone or in combination with verapamil (pa-tient 33). Exercise-induced "pleomorphic" ventriculartachycardia in the absence of coronary artery diseasehas been previously described.22,23

Short-term therapy of PVT. Short-term treatment withintravenous lidocaine was associated with inconsistentbenefit. This is in accord with the results reported byothers 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 therapyapplied (i.e., discontinuation of offending drugs, cor-

rection of electrolyte abnormalities, or pacing). Wefound (as has been emphasized by others with regard to

treatment of classic torsade de pointes3' 5) that cardiacpacing was uniquely effective in the management ofthese patients. The response to cardiac pacing was,

however, clearly unrelated to whether the QT was pro-

longed or not. We found that use of other type I antiar-rhythmic agents in patients with drug-induced PVTgenerally resulted in aggravation of the arrhythmia.While this would appear to be predictable, we are

unaware of any previous reports documenting thisfinding for patients with drug-induced PVT. In addi-tion, bretylium was also associated with arrhythmiaaggravation in three patients (Nos. 7, 20, and 25).

Long-term therapy for the original arrhythmia. Long-term amiodarone was initiated for control of the origi-nal arrhythmia in 12 patients with type I drug-inducedPVT. Long-term follow-up of this group revealed thatthe arrhythmia was controlled in all, but one patientdied suddenly 1 month after discharge from the hospi-tal. While our findings suggest that long-term therapywith amiodarone is not proarrhythmic in those withtype I drug-induced PVT, it should be emphasized thatamiodarone itself may cause PVT.'4 The exact inci-dence of PVT due to amiodarone is not known, butappears to be very low. In our total series of 460patients treated with amiodarone, only three instances(0.7%) of PVT were recorded. It should be empha-sized that the 0.7% incidence of PVT is a minimalfigure. The overall incidence of sudden death in our

experience for patients with malignant ventricular ar-

rhythmias treated with amiodarone is 8%,'5 and thetype of arrhythmia responsible for the sudden demise isnot known.QT interval and PVT. The role of the QT interval in

patients with PVT remains uncertain for several rea-

sons. First, precise measurement of the QT interval(even from 12-lead electrocardiographic tracings) willat times be difficult and the precise upper limits ofnormal and the suggested corrections of the QT inter-val for rate are controversial.24 In patients with drug-induced PVT, the issue is further compounded by theinherent 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 drug-

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OT durationA

0,70 -

0,65

0,60

Cj 0,55

0,50

0,45

0,40

0

00

U03: -

0,50 0,60 0,70 0,80 0,90 1;00 1,10 1,20

R-R INTERVAL secFIGURE 4. The effects of quinidine on the QT interval in 20 patientstreated with this drug. The QT interval in seconds is displayed on theordinate while the spontaneous sinus cycle length is shown on theabscissa. The QT interval varied from 0.35 to 0.62 sec. Four patientswho developed ventricular arrhythmias are represented by ringed cir-cles. Note that the QT interval proved to be an insensitive guide forpredicting development of PVT. In addition, in the group of patientswho did not develop ventricular arrhythmias, the QT interval fell be-tween 0.40 to 0.48 sec. These data were kindly provided by Drs.Orinius and Ejvinsson.

induced PVT fell into the range expected for thosetreated with type I agents but who never experiencedPVT* (figure 4). For this reason, in our study, thosepatients with drug-induced PVT were not consideredto have a clearly prolonged QT interval unless thisinterval exceeded 0.48 sec. Moreover, our data sug-gest that the QT interval cannot be used as a reliableguide for deciding on short- or long-term antiarrhyth-mic therapy in patients with PVT because (1) mostpatients with drug-induced PVT and a normal QTfailed to respond to other type I drugs, (2) cardiacpacing was almost universally effective regardless ofthe QT interval, and (3) long-term therapy with amio-darone proved effective in patients with type I drug-in-duced PVT and this therapy was usually associatedwith further lengthening of the QT interval.

Clinical implications. The most important finding ofour study was that PVT, whether associated with nor-mal or slightly prolonged QT intervals, was usuallydrug induced. Drug-induced PVT was almost alwayspreceded by sinus bradycardia or a pause, while this

*Orinius E: Personal communication.

finding was much less consistent in those with PVTthat was not drug related. We suspect that some of thepatients with drug-induced PVT were treated with oth-er type I agents, in part because either the QT intervalwas normal or the characteristic pattern of twisting ofthe QRS around an isoelectric line was not present. Wetherefore believe that the critical element in the propermanagement of these patients is recognition of thePVT pattern. Intravenous lidocaine was inconsistentlyeffective. Intravenous bretylium was ineffective andprobably proarrhythmic, while cardiac pacing was al-most universally effective in arrhythmia control, re-gardless of the QT interval. A 4 day hospital staywould be expected to detect approximately half of pa-tients susceptible to type I drug-induced PVT. In addi-tion, other possible aggravating causes, such as occur-rence of bradyarrhythmia, electrolyte disorders, use ofdiuretic agents, or cardiac surgery should be evaluat-ed. Our preliminary findings suggest that amiodaronemay prove to be a suitable therapeutic option for long-term control of the original arrhythmia in patients withdrug-induced PVT.

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Ward DE, Wellens HJJ: The minimally appropriate electrophysio-logic study for the initial assessment of patients with documentedsustained monomorphic ventricular tachycardia. PACE 8: 918,1985

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3. Soffer J, Dreifus LS, Michelson EL: Polymorphous ventriculartachycardia associated with normal and long Q-T interval. Am JCardiol 49: 2021, 1982

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P T Nguyen, M M Scheinman and J Segerinterval.

Polymorphous ventricular tachycardia: clinical characterization, therapy, and the QT

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