QT Syndrome and Concomitant Astemizole Ingestion

Br HeartJ 1993;70:469-470 469

CASE REPORTS Br Heart J: first published as 10.1136/hrt.70.5.469 on 1 November 1993. Downloaded from Cardiac arrest in a young woman with the long QT syndrome and concomitant astemizole ingestion

Paul Broadhurst, Anthony W Nathan

Abstract series of electrocardiograms and during these Ventricular fibrillation developed in a 19 it was noted that her QTc was persistently year old woman taking the antihistamine prolonged (table), though it did shorten with astemizole. She was successfully resusci- time. Astemizole has a long half-life (18-22 tated. QTc prolongation was found and days), but even 2 months after the drug had persisted despite withdrawal of the drug. been stopped the patient's QTc was still pro- Aggravation of congenital long QTc syn- longed at 463 ms (upper limit of normal3 gen- drome by astemizole is postulated. More erally accepted to be 440 ms). Both her caution should be exercised with the use father's and sister's QTc intervals were pro- ofthis drug. longed initially. They were both taking the antihistamine terfenadine at the time and (Br HeartJ' 1993;70:469-470) subsequent electrocardiograms taken in the drug-free state showed a QTc of 435 ms (the upper limit of normal) in the sister though Astemizole is an antihistamine that is widely QTc was still slightly prolonged in the father. used to treat hay fever. It antagonises the There was no family history of syncope or effects of histamine at the HI receptor site. It sudden death and there were no hearing is one of several drugs of this type and is problems in any family member. Echo- available without prescription. Over the past cardiography, cardiac catherisation and elec- few years there have been several reports of trophysiological investigation were carried out serious ventricular arrhythmias in patients in the patient. The results of these tests were taking astemizole.1 All, however, have been unremarkable. We concluded therefore that http://heart.bmj.com/ the consequence of taking the drug in actual our patient and her father both had the long or suspected overdose. We report a case in QT or Romano-Ward syndrome. which we postulate that astemizole con- The patient was discharged on atenolol 50 tributed to the development of ventricular mg twice daily and was well 6 months later. fibrillation in a young woman with what She takes beclomethasone intranasally for her transpired to be congenital long QT syn- hay fever and both she and her family have drome. been warned not to take antihistamines. on September 26, 2021 by guest. Protected copyright. Case report Discussion A 19 year old woman was admitted after a This case illustrates several interesting and cardiac arrest call from the nurses' swimming important points about the cardiac effects of pool. She had been swimming and after antihistamines, particularly in the long QT becoming short of breath got out of the pool, syndrome. The increasing number of serious fell back in and was then dragged out. rhythm disturbances reported with both terfe- Cardiopulmonary resuscitation was started nadine and astemizole has led to a warning and she was found to be in ventricular fibrillation. She was successfully defibrillated and over several days recovered completely with- QT, RR, and QTc intervals in the patient and herfamily out any neurological sequelae. Subject QT (ms) RR (ms) QTc (ms) The cause of her arrest was initially Patient on day: unclear. Asthma was implicated at presenta- 1 420 740 488 but she was easy to ventilate and subse- 4 540 940 557 tion, 7 540 1090 519 quent pulmonary function tests were normal 11 425 890 452 Department of and a histamine provocation test was nega- 17 390 765 448 Cardiology, 19 370 835 406 St Bartholomew's tive. She had been prescribed (by her general 20 410 805 456 was astemizole 20 Hospital, London practitioner) and taking mg Father 445 910 468 P Broadhurst per day, twice the maximum recommended Off terfenadine 440 920 459 A W Nathan dose, and had been doing so for several weeks Mother 350 690 412 400 640 500 Correspondence to: were aware that this Sister Dr Anthony W Nathan, because of hay fever. We Off terfenadine 410 890 435 Department of Cardiology, drug has been implicated in the genesis of St Bartholomew's Hospital, QTc is the QT interval corrected for heart rate using Bazett's West Smithfield, London ventricular arrhythmias. formula.2 The intervals of the patient on the days after the EClA 7BE. Cardiological investigations included a admission are also shown. 470 Broadhurst, Nathan

being issued by the Committee on Safety of treat this young, very active woman with,B Medicines.' When these drugs are taken in blockers, possibly for life. Because QTc pro- deliberate overdose the risks are clear but it longation persisted after withdrawal of the seems that drugs that interfere with the drug we felt that this approach was justified. Br Heart J: first published as 10.1136/hrt.70.5.469 on 1 November 1993. Downloaded from metabolism of these antihistamines also pose Worldwide experience with /3 blockers in this a risk.4 The administration of astemizole in rare condition suggests that such treatment is twice the recommended dosage in our patient beneficial in reducing the incidence of tor- with underlying QT interval prolongation sades de pointes, syncope, and sudden probably predisposed her to ventricular fibril- death.8 lation: periods of sympathetic activation such After our experience and that of others, it as occur with exercise (for example, swim- might be advisable to reappraise the general ming) are also recognised as a precipitating availability of antihistamines. We endorse the factor.5 Furthermore in another family mem- warning of both the manufacturers and the ber the administration of terfenadine pro- Committee on Safety of Medicines never to duced QTc prolongation that was not exceed the recommended dose. apparent in the drug free state. The cardiac electrophysiological effects of antihistamines have not been described, though in a small 1 Ventricular arrhythmias due to terfenadine and astemi- group of volunteers QT prolongation did not zole. Current Problems. London: Committee on Safety of Medicines 1992;35:1-2. occur when astemizole was administered in 2 Bazett HC. An analysis of the time relations of electro- therapeutic doses.6 Animal studies showed H, cardiograms. Heart 1920;7:353-70. 3 Moss AJ, Schwartz PJ, Crampton RS, et al. The long QT histamine receptors within the heart.7 syndrome. Circulation 1991;84:1136-44. Blockage of these receptors might be 4 Pohjola-Sintonen S, Viitasalo M, Toivonen L, Neuvonen P. Torsades de pointes after terfenadine-itraconazole expected to accelerate conduction in cardiac interaction. BMJ 1993;306:186. tissue in response to any endogenous hista- 5 Roden DM. The long QT syndrome and Torsades de Pointes: Basic and clinical aspects. In: El-Sherif N, mine, for example to increase the speed of Samet P, eds. Cardiac pacing and electrophysiology. conduction within the atrioventricular node. Philadelphia: WB Saunders, 1991;265-84. 6 Craft TM, Vanden Bussche G, De Cree J, Griffiths JV. It is difficult to see how such electrophysio- ECG studies with astemizole. Hum Exp Toxicol 1987;6: logical effects might be expected to produce 527-8. 7 Levi R, Kuye JO. Pharmacological characterisation of car- QTc prolongation, which is generally accep- diac histamine receptors: sensitivity to H,-receptor ted as being due to abnormal repolarisation. antagonists. EurJ Pharmacol 1974;27:330-8. 8 Moss AJ, Schwartz PJ, Crampton RS, Locati E, Carleen From a practical point of view, we were left E. The long QT syndrome: a prospective international with the dilemma as to whether we should registry. Circulation 1985;71:17-21. http://heart.bmj.com/ on September 26, 2021 by guest. Protected copyright.