958 BRIEF REPORTS NonfatalAjmaline Cardiotoxicity VICTOR MEDINA-RAVELL, MD LUIS RODRIGUEZ-SALAS, MD IVAN J. MENDOZA, MD AGUSTIN CASTELLANOS, MD Ajmaline, a class I antiarrhythmic agent, has been used extensively for many years in Europe and South America, mainly for diagnostic purposes.1-6 Although the relatively low dose recommended by Wellens and co-workers (50 mg) is usually safe, nevertheless these investigators reported an instance of sudden death.3p4 In this report we discuss the findings in 2 patients in whom nonfatal toxicity developed with small doses of ajmaline. zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA An ajmaline test to expose latent atrioventricular (AV) block was performed in 2 patients. One of the patients w as also evaluated with invasive electrophysiologic techniques. Both had syncope of unexplained origin, complete right bundle branch block with normal electrical axis and normal PR interval, chronic chagasic cardiomyopathy, cardiomeg- aly, compensated heart failure, and normal renal func- tion. The test was performed in the cardiovascular laboratory after all medications had been discontinued for 24 hours. The procedure was explained, and each patient gave informed consent. Ajmaline* (50 mg) was injected intravenously over 3 minutes in Case 1 and over 2 minutes in Case 2. Both pa- tients had catheter electrodes in the right ventricle to provide “on- demand” pacing if necessary. In Case 1 (age 59years; weight 75 kg), 3:2 type II (Mobitz) AV block, abnormal left-axis deviation and a 34% increase in QRS duration (Fig. 1) developed. Ajmaline toxicity, mani- fested by a unifocal ventricular tachy cardia, occurred 3 minutes later (Fig. 2, top). Therefore, a bolus of 100 mg of i.v. lidocaine wasgiven. One minute later, after a decrease in rate to 100 beatslmin and a change in QRS morphology, the ventricular tachy cardia stopped and the pacemaker took over (Fig. 2, middle). Sinus rhy thm with a prolonged PR interval and 1:l AV conduction reappeared 1 minute later (bottom). Ten minutes after the end of the injection, the electrocardiographic characteristics were similar to those before ajmaline was given. In Case 2 (age 53 years, weight 80 kg), ajmaline toxicity developed 3 minutes after the end of the injection (Fig. 3, right). The His-Purkinje conduction time increased 125% (HV interval of 90 ms). There was a prolongation in intra- ventricular conduction time: QRS duration increased 66% (to 200 ms) and the left septal-to-right ventricular apex conduction time interval increased 200% (to 150 ms). A pattern of true, or false, ‘injury” (abnormal ST- segment elevation) occurred in chest lead VI.~ These abnormalities gradually disappeared (without any intervention) over 12 minutes, at which time the recordings were similar in all respects to those obtained before ajmaline administration. l Ajmaline (crystalized alkaloid) Medicamentos York, SA (Inverni and Della Beffa), Milan, Italy. From the Fundacion Cor, Valencia, Venezuela, and the Division of Cardiology, Department of Medicine, University of Miami School of Medicine, Miami, Florida 33101. Manuscript received September 14, 1983; revised manuscript received November 17, 1983, accepted November 23, 1983. Pacemakers were not implanted immediately after the study. Howeuer, symptomatic, paroxysmal, AV block was documented subsequently in both patients. Therefore, they were treated with permanent AV sequential (DVI) pace- makers. Ajmaline toxicity has been related to several factors: amount and speed of injection, renal function (the drug is eliminated through the urine), type of ajmaline (toxicity is greater with a propylajmaline base than with a chloracetylajmaline base), and severity and origin of underlying heart disease (the drug is definitely con- traindicated in acute myocardial infarction).6 Toxicity reportedly is low with therapeutic doses of ajmaline (1 mg/kg).l-37s In a recent discussion of 1,260 ajmaline tests performed in their institution, Perrot et al2 observed nonsustained ventricular tachycardia in 6 patients and ventricular fibrillation in 1 patient. Se- rious side effects with total doses of 50 mg of ajmaline are even more rare. 3,4,6Therefore, it is important to consider why death occurred in the case of Wellens et al and why toxicity was seen in the 2 patients discussed in this communication.4 Wellens et al4 believed that ajmaline should not be given to patients with hypertrophic cardiomyopathy. They believed that their patient may have died because the conduction-delaying and slightly negative inotropic action of ajmaline in the setting of hypertrophic car- diomyopathy could have initiated a ventricular ar- rhythmia resulting in the catastrophic sequence of events. In our Case 1, ventricular tachycardia could have been a bradycardia-dependent arrhythmia appearing during the periods of ventricular slowing resulting from the ajmaline-induced type II (Mobitz) AV block. In Case 2, toxicity may have been related to the time taken to administer the drug (2 minutes), which was shorter than that recommended by Brugada et aIs and Wellens et al4 (3 minutes). However, the ajmaline toxicity in our 2 cases may have reflected the deleterious side effects that any class I antiarrhythmic agent may have in patients with car- diomegaly and congestive heart failure. We could not determine whether this was due to the specific cause of the underlying heart disease (chronic chagasic cardio- myopathy). Therefore, further studies are required to evaluate if toxicity with relatively small doses of ajma- line occurs in patients with organic heart disease of other causes. 1. Guhl CL, Co& A, Valh PE, Tricot R. L’epreuve a I’ajmalinedarts le di- a r ostic du bloc auriculo-ventriculaire paroxystique. Arch Ma1 Ccaur 1 .73;10:1241-1253. 2. Perroi B, Alloi E, G@enkrantz JM, Cherrier F, Falvre G. Ex loration endc- cavltalre hisienna.Apportsdu test a l’ajmaline. Rev Port z ardlol 1983;2: zyxwvutsrqp 31S_!XA _-- ..“.. 3. Fugada P, Da8een WR, Braat S, Gorfpls AP, Wellens HJJ. Value of the a)maline-pfocainarnkla testto predict tba effactof tongterm cral amialarone on tha anterograds effective refractoryperiodof the accessorypathwayin tha Wolff-Parkinson-White syndrome. Am J Cardiol 1983;52:70-72. 4. Wekns HJJ, B&I FW, Vauql EJ. Death aftar ajrnalins administration. (letter to tha editor).Am J Cardiol 1980;45:905. 5. Chlale PA, Przybylski J, Lalno RA, Haloern k, Sanchek RA, Gabrlell A, Ellreii MV, Roeenbaum MB. Electrocardiographic changes evckad by ajmallne In chronic Chagas’ disease withoutmanifest myocarditis. Am J Cardlol 1982;49: 14-20. 8. Punch P. Ajmallne. In: Bayes A, CosinJ. sds. Diagnosis and Treatmentof CardiacArrhythmias. New York: Pergamon Press, 1980:807-820.