a prenylamine toxicity showing pointes phenomenon...

Postgraduate Medical Journal (June 1981) 57, 381-384

A case of prenylamine toxicity showing the torsade de pointesphenomenon in sinus rhythm?

COLIN I. MEANOCK*M.B. B.S.

MARK I. M. NOBLED.Sc., M.D., Ph.D., F.R.C.P.

King Edward VII Hospital and The Midhurst Medical Research Institute

SummaryA case of torsade de pointes attributed to prenylamineis described. In addition, the authors show QRS axisvariation of a similar nature in sinus rhythm. It ispostulated that these changes of QRS axis direction,seen in ventricular tachycardia and sinus rhythm, areboth manifestations of partial refractoriness, withinthe ventricle, producing gross changes in the meanQRS vector.

IntroductionThe adverse effects of the anti-anginal drug

prenylamine (Synadrin), involving the sequelae ofQ-T prolongation, have been widely reported inEurope (Picard, Anzepy and Chauvin, 1971; Benset al., 1973; Jacovella and Vajola, 1976), but onlyoccasionally in England (Puritz et al., 1977). Themode of action of prenylamine is claimed to bereduced sympathetic stimulation by its effect oncatecholamine uptake and release, in addition to adirect coronary dilating effect (Wade and Reynolds,1977).A case is now reported of repeated episodes of

ventricular tachycardia attributed to prenylamine,and the arrhythmias produced are examined.

Case reportA 55-year-old woman, known to have had rheu-

matic fever at the age of 7 years and again at the ageof 14 years, was treated with prenylamine following2 episodes of 'wooziness' and sensations of heavinessdown the left arm. She had been asymptomatic untilthis time, and her ECG was normal.

After starting treatment she experienced approxi-mately monthly attacks of vertigo and rapid palpi-tation unassociated with any precipitant factors.One month before admission the frequency of

attacks increased and became associated with black-out and urinary incontinence. The day of admissionthe patient had experienced 5 such attacks at home.

* Reprint requests: The Midhurst Medical ResearchInstitute, Midhurst, West Sussex GU29 OBL.

On arrival at hospital she was fully conscious,with no signs of general systemic illness. Pulse wasirregular, rate 88/min, with a BP of 150/90 mmHg.There were signs of mixed mitral valve disease, withno evidence of heart failure. Serum potassium onadmission 42 mmol/l. The patient admitted totaking prenylamine in therapeutic doses up to heradmission.

Shortly after admission, whilst having an ECG,the patient became unconscious, with a weak andrapid pulse. The synchronous ECG recording leads1, 2 and 3 (Fig. l(a)) shows a ventricular tachycardiawith the torsade de pointes (MacWilliam, 1923;Dessertenne, 1966) or twisting peak phenomenondisplayed in lead 3. This episode reverted to sinusrhythm following a bolus of 100 mg of i.v. lignocaine.An electrocardiogram, taken between 2 such epi-sodes, showed sinus rhythm with multifocal ventricu-lar ectopics, grossly prolonged Q-T interval at0-72 sec and wide irregular T waves.Although this patient's situation was not initially

attributed to prenylamine, the drug was withdrawnon admission.Over the next 6 days, the phenomenon of rotating

frontal plane axis in sinus rhythm was displayed(Figs 2, 3). Following this, the patient settled to astable sinus rhythm with her Q-T interval returningto normal at 0-40 sec. There was no historical orenzymatic evidence of myocardial infarction, andshe was discharged home feeling well on the 13thday.

DiscussionThe torsade de pointes phenomenon is a distinct

form of ventricular tachycardia characterized byQRS polarity oscillation over short runs of beats(Fig. l(a)). It is typically found in ventriculartachycardia associated with Q-T prolongation, andhas been clearly described before (Krikler andCurry, 1976). It is important to note that drugs suchas lignocaine which act by increasing repolarizationtime, can themselves cause this arrhythmia, and

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382 Case reports

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FIG. 1. (a) synchronously recorded ECG leads 1, 2 and 3 during ventricular tachycardia with torsade de pointes. (b) mean QRSvector plotted on Einthoven's triangle for beats A-E showing progressive counter-clockwise rotation.

therefore a drug such as isoprenaline which shortensrepolarization time is the theoretical pharmaco-logical treatment of choice (Krikler and Curry,1976).The authors show 2 further cardiographic

abnormalities attributed to the use of this drug.Firstly, the way in which, even in sinus rhythm, thecomplexes became equiphasic and then the QRS axischanged direction (Fig. 2). This was the dominantabnormality of days 2 and 3 of the patient's admis-sion. Secondly, the continuing change of the frontalplane vector (Fig. 3) seen over the first week ofadmission. The appearances in Fig. 3 taken on theirown are compatible with an alternating hemiblock.However, in conjunction with the progressive axisrotation implied by the monitor lead (Fig. 2), it isthought that the changes in Fig. 3 are more likelyto be due to such axis rotation. It is unfortunate thatfull 12-lead ECGs could not be taken during theprogressive changes recorded from the bedsidemonitor. Furthermore, no ECG changes such asthose recorded in Fig. 3 were ever observed beforeor after the patient's illness, which resolved followingwithdrawal of prenylamine.

In an attempt to understand these changes, thesynchronous recording of leads 1, 2 and 3 duringthe ventricular tachycardia displaying the torsade de

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FIG. 2. Chest monitor lead '1' showing rotation offrontal plane vector in sequential QRS complexes as intorsade de pointes.

pointes was used to plot the frontal plane vectors forsuccessive beats. Although it is difficult to establishan isoelectric line with accuracy, the estimated vec-tors indicated an ordered anticlockwiEe rotation inthe frontal plane (Fig. 1(b)).

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Case reports

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384 Case reports

The prolonged QT interval in sinus rhythm indi-cates delayed repolarization and increased refractoryperiod. There is also greatly increased variance ofrepolarization time indicated by the wide irregularT waves. Partial refractoriness in certain areas of theventricle is presumably sometimes still present aftera normal R-R interval, producing a gross change inmean QRS vector between sinus beats (Fig. 2).This phenomenon is greatly exaggerated duringtachycardia (torsade de pointes, Fig. 1). Here thespread of repolarization times produced a progres-sive anticlockwise rotation of the mean direction ofelectrical forces during sequential depolarization(Fig. 1(b)).

ReferencesBENS, J.L., DUBOISSET, M., QUIRET, J.C., LESBRE, J.P. &

BARNASCONI, T. (1973) Syncopes par torsades de pointes

induites ou favorisees par la prenylamine. Archives desmaladies du coeur, des vaisseaux et du sang, 66, 1427.

DESSERTENNE, F. (1966) La tachycardie ventriculaire a deuxfoyers opposes variables. Archives des maladies du coeur,des vaisseaux et du sang, 59, 263.

JACOVELLA, G. & VAJOLA, F.S. (1976) Effetti sfavorevoli deifarmaci; sincope da prenilamina. Giornale italiano dicardiologia, 6, 547.

KRIKLER, D.M. & CURRY, P.V.L. (1976) Torsade de pointes,an atypical ventricular tachycardia. British Heart Journal,38, 117.

MACWILLIAM, J.A. (1923) Some applications of physiologyto medicine. II. Ventricular fibrillation and sudden death.British Medical Journal, 2, 215.

PICARD, R., ANZEPY, P. & CHAUVIN, J.P. (1971) Syncopesi repetition au cours d'un traitement prolonge par laprenylamine (Segontine 60). Presse Medicale, 79, 145.

PURITZ, R., HENDERSON, M.A., BAKER, S.N. & CHAMBERLAIN,D.A. (1977) Ventricular arrhythmias caused by prenyl-amine. British Medical Journal, 2, 608.

WADE, A. & REYNOLD, J.E.F. (1977) Martindale. The ExtraPharmacopoeia, 27th edn. The Pharmaceutical Press,London.

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