Efficacy and tolerance of tocainide during long-term treatment of malignant ventricular arrhythmias

A group of 51 patients with malignant ventricular arrhythmias refractory to standard oral antiarrhythmic agents were treated with oral tocainide. Antiarrhythmic efficacy was defined as total abolition of occurrences of ventricular tachycardia (VT) or ventricular fibrillation (VF) as assessed by hospital admissions for arrhythmias and the occurrence of sudden cardiac death (SCD). Of the 51 patients, 32 (63%) initially tolerated tocainide and were discharged from the hospital. Of the 19 patients not initially responding to tocainide, 6 (12%) had arrhythmia recurrence and 13 (25%) developed intolerable central nervous system or gastrointestinal side effects. Of these 19 short-term nonresponders, 8 (42%) patients suffered SCD over an average follow-up of 24 months (annual SCD rate of 21%). Two patients suffered SCD during the first week of tocainide therapy. Discounting the 2 patients with SCD on tocainide therapy, 6 of 17 (35%) patients initially withdrawn from tocainide suffered SCD (annual SCD rate of 18%). Twenty-four of the 32 short-term responders did not have arrhythmia recurrence over a mean follow-up of 38 months resulting in an overall long-term efficacy of 47% (24/51). Over an average follow-up of 38 months for these 24 short-term responders, 12 patients expired from nonarrhythmic causes, 3 patients were withdrawn for non-drug-related causes, and 9 patients remain on tocainide therapy. Of the 8 long-term nonresponders, 3 patients had arrhythmia recurrence and died suddenly while 5 patients developed intolerable side effects. The annual SCD rate in short-term responders was 3%. Eighteen of the 51 patients (35%) were withdrawn from the study because of adverse effects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Chronic tocainide therapy for refractory high-grade ventricular arrhythmias

Tocainide, an oral analog of lidocaine, was evaluated as a long-term antiarrhythmic agent in 21 patients with symptomatic complex ventricular ectopic activity (10 with hemodynamically significant ventricular tachycardia) refractory to currently available antiarrhythmics singly, and in combination for periods of 3 days to 35 months (mean 13.6 months). Tocainide appeared to be an effective and safe agent for the control of these refractory symptomatic ventricular arrhythmias in 14 of the 21 patients (66%). Minor central nervous system and gastrointestinal side effects were present in most of the patients, usually early on in therapy, and only precluded long-term use in 2 patients. Furthermore, lidocaine responsiveness was a good predictor of tocainide effectiveness in this group of patients. Tocainide precipitated atrioventricular (A-V) block in one patient with pre-existing A-V nodal disease; two patients developed a skin rash while on tocainide therapy. These two patients had previously developed lupus-like syndromes and skin rashes while on procainamide. The ANA titers had been falling in these two patients while on tocainide, and in one of these patients with true systemic lupus erythematosus, rechallenge with tocainide failed to produce skin rash. Tocainide's long plasma half-life and high oral bioavailability permit an 8-h regime. We conclude that tocainide is an effective, safe antiarrhythmic agent with tolerable side effects.     

Randomized double-blind study of intravenous tocainide versus lidocaine for suppression of ventricular arrhythmias after cardiac surgery

To compare the therapeutic efficacy and safety of intravenous tocainide with that of intravenous lidocaine in patients with ventricular arrhythmias after cardiac surgery, 25 patients were randomized to either agent in a double-blind manner. Tocainide was given in 16 patients as a 250 mg bolus followed by a loading infusion of 500 mg over 15 minutes and a maintenance infusion of 33.3 mg/min. Lidocaine was administered in 9 patients as a 100 mg bolus followed by a loading infusion of 60 mg over 15 minutes and a maintenance infusion of 1.4 mg/min. Therapy was continued for 24 hours in initially responding patients. With analysis of 24-h taped electrocardiograms it was found that single premature ventricular complexes (PVCs) were suppressed by tocainide by more than 80% in 94% of patients and by lidocaine in 75% of patients (p = NS). Couplets and ventricular tachycardia events were eliminated in all patients by either drug. Multiform PVCs were abolished in 94% of the patients after tocainide and in 75% after lidocaine (p = NS). Average overall success over the 24 hours with more than 80% suppression of single PVCs and simultaneous elimination of higher forms of arrhythmia was 71% with tocainide and 59% with lidocaine (p = NS). Adverse effects were negligible, with only one patient in the lidocaine group developing diaphoresis without necessitating termination of therapy. Treatment rapidly produced and then maintained blood levels of 4-10 mg/l for tocainide and 1-4 mg/l for lidocaine. We conclude that intravenous tocainide is well tolerated and has comparable efficacy to lidocaine in the acute therapy of postcardiac surgery ventricular arrhythmias.     

Spontaneous right ventricular outflow tract tachycardia in a patient with Brugada syndrome

We report the case of a 28-year-old man with no structural heart disease, who exhibited clearly augmented ST segment elevation in the right precordial leads, followed by induction of spontaneous right ventricular outflow tract tachycardia with intravenous administration of Class IA antiarrhythmic drugs. The electrophysiologic mechanism of this tachycardia was thought to be triggered activity due to delayed afterdepolarizations. Due to the existence of substrates that were similar to Brugada syndrome combined with right ventricular outflow tract tachycardia, this case may represent a subtype of Brugada syndrome.     

Serial electrophysiological testing of antiarrhythmic drug efficacy in patients with recurrent ventricular tachycardia

The purpose of the present study was to determine the predictivevalue of serial electrophysiological testing during antiarrhythmictherapy in patients with recurrent ventricular tachycardia and/orventricular fibrillation in regard to symptomatic status andoutcome. Eleven patients (ten male, one female, mean age 54 ±10 years, mean ± S.D.J with recurrent ventricular tachycardiawere studied. Mean ejection fraction was 34 ± 12%. Mostpatients suffered from coronary artery disease. The median durationof recurrent ventricular tachycardia before the study was 12weeks (minimum one week, maximum 16 years). In seven patientsbetween one and 61 cardioversions had been performed beforethe study to terminate ventricular tachycardia. Ventricular tachycardia could be initiated by programmed rightventricular stimulation in all patients. After control recordingshad been obtained, the stimulation tests were repeated duringantiarrhythmic therapy until an effective regimen was found.The following drugs were used in this sequence: disopyramide,mexiletine, propafenone, aprindine plus beta-adrenergic blockingdrugs and digitalis. In three patients, there was no change in the inducibility ofventricular tachycardia during therapy whereas in eight patients,ventricular tachycardia was more difficult to induce or no longerinducible. Patients were followed at regular intervals (meanfollow-up time 41 ± 22 weeks). In those three patientsin whom ventricular tachycardia was still inducible, two suddendeaths occurred; one patient was referred to surgery becauseof persistent spontaneous and inducible attacks of ventriculartachycardia despite antiarrhythmic therapy. No cardiac deathoccurred in the eight patients in whom ventricular tachycardiawas more difficult to induce or no longer inducible. All patientswere asymptomatic, and had no recurrence of their ventriculartachycardia in their Hotter ECGs. Thus far, serial electrophysiological testing has been usefulin predicting antiarrhythmic drug efficacy in patients withrecurrent ventricular tachycardia. It may help to prevent suddendeath in these highly endangered patients.     

Treatment of ventricular arrhythmias with oral tocainide

This is a report of a multicenter open study of the use of tocainide, a new lidocaine-like antiarrhythmic with a high oral bioavailability, in the treatment of life-threatening ventricular arrhythmias refractory to other therapy. The majority of patients have received 1,200 to 2,400 mg daily in divided doses and have been treated for over 6 months and some for longer than 3 years. Overall, 61% of the patients responded successfully to tocainide therapy. In the 252 patients with documented, severe, symptomatic arrhythmias, 71% responded, and the majority (87%) showed a total abolition of symptomatic events. Gastrointestinal and central nervous system events were the most common adverse experiences, and 11% had to discontinue therapy; however, the remaining 89% tolerated tocainide satisfactorily.     

Tocainide and metoprolol: an efficacious therapeutic combination in the treatment of premature ventricular beats

A double-blind crossover study was performed in 20 patients to verify the efficacy of tocainide plus metoprolol in patients with premature ventricular contractions (PVCs) class Lown greater than or equal to 2 (mean frequency greater than or equal to 30/h) judged as being "stable" by at least three basal 24-h Holter ECGs with PVC variation of less than +/- 25%. All 20 patients were submitted to a placebo period; and all were subsequently randomized to therapy with tocainide 1800 mg/day or metoprolol 200 mg/day for 15 days and then to tocainide 1800 mg + metoprolol 200 mg/day or tocainide 1200 mg + metoprolol 200 mg/day for 15 days, followed by a crossover of the two combination treatments. At steady state in every stage we controlled for plasma levels of the drugs, a 24-h Holter recording, and a 12-lead ECG. A modified Lown score was evaluated together with the Lown class. Tocainide (mean plasma level 3.3 +/- 0.7 micrograms/ml) was efficacious in 3 of 8 patients, the modified Lown score decreased from 63 +/- 32 (placebo period) to 42 +/- 27 (p less than 0.01) and Lown 4B arrhythmias were abolished in 3 of 4 patients. Metoprolol (mean plasma level 97.4 +/- 89.6 ng/ml) was efficacious in 2 of 10 patients; the modified Lown score and Lown classes did not change significantly. Administration of tocainide 1200 mg + metoprolol 200 mg obtained a positive response in 9 of 12 patients, the modified Lown score decreased significantly compared with placebo (from 53 +/- 31 to 32 +/- 30, p less than 0.01) and Lown 4B arrhythmias were abolished in 2 of 5 cases. Tocainide 1800 mg plus metoprolol 200 mg was scarcely tolerated owing to neurologic and gastroenteric side effects, and only three patients completed this stage with no better antiarrhythmic results compared to the lower dose. In conclusion, the combination of tocainide at 1200 mg and metoprolol 200 mg is well tolerated, efficacious in a high percentage of patients, and superior to single drug therapy in patients with stable PVCs.     

Idiopathic verapamil-sensitive left ventricular tachycardia complicated by right ventricular outflow tract ventricular tachycardia and ventricular fibrillation.

Idiopathic ventricular tachycardias (VTs) are generally divided into those arising from the right ventricle and those arising from the left ventricle. There has been few reports of two morphologically distinct VT occurring in patients with no apparent structural heart disease. We report a patient with verapamil-sensitive left VT with a right bundle branch block pattern that spontaneously changed to VT with a left bundle branch block pattern. Ventricular fibrillation was induced by the application of programmed stimulation. Although it is unclear if our patient with pleomorphic VT has ventricular vulnerability, it is necessary to investigate further and follow him carefully.     

Initiation of ventricular tachycardia by interpolated ventricular premature depolarizations

Programmed electrical stimulation of the heart was performed in a 47 year old man with prior myocardial infarction and recurrent sustained ventricular tachycardia that was refractory to standard medical therapy. The tachycardia could be provoked by regular atrial pacing at a rate of 100/min, regular ventricular pacing at the same rate and regular atrial pacing at a rate of 200/min in the presence of 2:1 atrioventricular block. All three techniques resulted in an interval of approximately 600 ms between successive ventricular depolarizations. Single interpolated ventricular premature depolarizations delivered during sinus rhythm were followed by a postextrasystolic conducted sinus beat that initiated ventricular tachycardia. However, when the same interpolated ventricular premature depolarization was followed by a ventricular fusion beat no tachycardia ensued. This study therefore emphasizes the importance of heart rate and the pattern of ventricular activation in determining whether ventricular tachycardia can be provoked by programmed electrical stimulation of the heart.     

Slow ventricular tachycardia caused by naftidrofuryl overdose (naftidrofuryl and ventricular tachycardia)]

Treatment with intravenous naftidrofuryl may be complicated by ventricular arrhythmias. A case of slow ventricular tachycardia occurring in a 65-year-old man with a dilated cardiomyopathy following an accidental overdose of naftidrofuryl (2 x 200 mg ampules in 250 ml of 5% glucose solution in 2 hours) prescribed for complicated arterial disease of the lower limbs is reported. This sustained ventricular tachycardia converted spontaneously after several hours. This case emphasises the risk of arrhythmogenic effects of this drug and indicates the need for careful monitoring when it is used intravenously in patients with underlying heart disease.     

心动过速终止后短暂心室复极异常和严重室性心律失常

目的 观察长时间心动过速终止后对心室复极和恶性室性心律失常发生的影响.方法 3例长时间心动过速(9 d～6个月)患者,两例为长时间发作室性心动过速(室速),其中1例为无休止性左心室特发性室速并诱发心动过速性心肌病;另1例为主动脉瓣换瓣术后5年发生束支折返性室速;第3例为持续性心房扑动伴心功能不良并因三度房室阻滞于10年前植入单腔起搏器.结果 3例患者在心动过速时并无晕厥和恶性室性心律失常发生,而在心动过速间隙或射频导管消融终止后均出现qr间期延长和恶性心律失常,其中1例持续心房扑动合并心力衰竭的患者最后死于多脏器功能衰竭;另两例室速射频导管消融治疗后1周QT间期逐渐恢复正常,分别随访20和39个月无室速和晕厥发作.结论 长时间心动过速后可导致短时间心室复极异常及恶性室性心律失常,应加强防范,防止发生心脏性猝死.     

Entrainment of ventricular tachycardia by atrial depolarizations

Four patients in whom rapid atrial pacing resulted in transient entrainment of a sustained ventricular tachycardia (VT) are reported. Ventricular fusion was seen in 3 of the 4. The following new observations were made: (1) A single atrial depolarization resulted in ventricular fusion and resetting of a VT, while atrial pacing at a faster rate entrained the same VT but without detectable fusion. This suggests that fusion during entrainment may be a rate-dependent phenomenon. (2) The interval between the last paced beat and the first nonpaced VT beat was different from the pacing cycle length in 3 patients. Two mechanisms accounted for this: the initial forces of each entrained QRS occurring as a result of the pacing wavefront, with fusion taking place only during the terminal forces, and the last entrained cycle exceeding the pacing cycle length by an amount related to the nonfused portion of the QRS, and delay in the presumed reentrant circuit responsible for the tachycardia. One VT was entrained with atrial pacing while ventricular pacing at the same rate resulted in termination, suggesting "site specificity" for termination. It is concluded that entrainment can occur without the criteria previously described as characteristic of it and that additional phenomena may be observed after stimulation that further support reentry as the mechanism of VT.