Amiodarone: risk factors for recurrence of symptomatic ventricular tachycardia identified at electrophysiologic study

Ventricular tachycardia induced by programmed electrical stimulation during amiodarone therapy often does not preclude a good clinical response. The purpose of this study was to determine whether use of discriminant analysis could distinguish patients who remained asymptomatic from those who subsequently developed symptomatic ventricular tachycardia or cardiac arrest. Studies were performed in 37 patients with sustained ventricular tachycardia who still had ventricular tachycardia induced during programmed electrical stimulation during amiodarone therapy. The mean follow-up time was 14.1 +/- 1.3 months (+/- SEM). Twenty-three patients remained asymptomatic, whereas 14 patients had symptomatic recurrence of their ventricular tachycardia. In patients with recurrence of arrhythmia compared with asymptomatic patients, administration of amiodarone caused a longer ventricular effective refractory period (296 +/- 8 versus 271 +/- 7 ms, p less than 0.05) and a greater change in corrected QT [QTc] interval (90 +/- 18 versus 44 +/- 9 ms, p less than 0.02), but no difference in the decrease in premature ventricular complexes after treatment with amiodarone. During amiodarone therapy, nonbundle branch reentrant repetitive ventricular responses were induced by a single ventricular extrastimulus during sinus rhythm in 9 of 14 patients with recurrent arrhythmias compared with 2 of 21 asymptomatic patients (p = 0.001). Also, less aggressive pacing techniques were required to induce ventricular tachycardia in 9 of 14 symptomatic patients compared with 4 of 23 asymptomatic patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term clinical outcome of ventricular tachycardia or fibrillation treated with amiodarone

The determinants of long-term clinical outcome were studied in 42 patients with recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) who were treated with amiodarone as the sole antiarrhythmic agent. Of the 42 patients, 11 (26%) either died suddenly or had recurrent, symptomatic, sustained VT during a mean follow-up period of 10 months (range 0.3 to 45). Of the 19 patients without inducible VT/VF during electrophysiologic study while receiving amiodarone, 1 patient died suddenly but no patient had recurrent VT/VF. Ten of the 23 patients (43%) with persistently inducible arrhythmia have died suddenly or have had recurrent VT/VF. Using survival and stepwise logistic regression analyses, 2 significant independent predictors of recurrent arrhythmia were identified; persistently inducible VT during electrophysiologic testing in patients receiving amiodarone therapy (p < 0.002) and the left ventricular ejection fraction at rest (p < 0.05). The predictive accuracy of the response to serial electrophysiologic testing during amiodarone therapy was 67%, the sensitivity was 58% and the specificity was 91%. Thus, serial electrophysiologic testing is useful for determining the prognosis in patients with inducible VT/VF treated with amiodarone.     

Clinical efficacy and electrophysiology of imipramine for ventricular tachycardia

Invasive electrophysiologic studies were performed before and during treatment with imipramine in 18 patients with inducible ventricular tachycardia (VT). All received imipramine, 50 mg twice daily for 3 days, and then 100 mg twice daily for 3 days. Imipramine increased the infranodal conduction times (HV) (from 58 +/- 7.8 to 65 +/- 10 ms) and QRS duration (from 133 +/- 21 to 153 +/- 39 ms) and significantly decreased sinus cycle length (from 875 +/- 145 to 711 +/- 116 ms) and maximal corrected sinus nodal recovery time (from 457 +/- 656 to 380 +/- 603 ms). The Wenckebach cycle length tended to decrease and the QT interval to increase, but these changes were not statistically significant. Atrial and ventricular refractory periods, atrioventricular nodal conduction times and induced VT cycle length did not change significantly. Imipramine prevented induction of VT in 2 patients, and VT was more difficult to induce in 1 patient. These 3 patients received chronic imipramine therapy. The 2 patients in whom no VT could be induced while taking imipramine have had no recurrence of arrhythmia at 6 and 12 months of follow-up. The third patient died suddenly 4 months after discharge from the hospital. One patient had worsening of arrhythmias while taking imipramine and 61% had minor adverse effects. The mean combined plasma imipramine and desmethylimipramine concentration at the time of the repeat electrophysiologic study was 227 +/- 114 ng/ml. Imipramine is effective against VT in some patients; however, like other type I antiarrhythmic drugs, the rate of efficacy is low.     

Clinical and electrophysiologic assessment of oral flecainide acetate for recurrent ventricular tachycardia: Evidence for exacerbation of electrical instability

Four patients with recurrent, symptomatic ventricular tachycardia (VT) refractory to conventional antiarrhythmic agents were given flecainide acetate to control arrhythmias. Ventricular stimulation studies were performed in all patients before and 1 to 2 weeks after initiation of oral flecainide therapy. Before flecainide, all patients had easily inducible VT that was morphologically identical to their spontaneously occurring arrhythmia. Flecainide increased the mean PR interval (from 0.17 to 0.23 second), mean QRS duration (from 0.08 to 0.12 second) and mean ventricular effective refractory period (from 235 to 270 ms). Mean corrected QT interval did not change (0.51 second).In 2 patients, VT could not be induced during follow-up stimulation studies. One patient has been treated successfully for 10 months, with no clinically apparent episodes of VT. One patient had recurrent nonsustained VT and was withdrawn from the study as a treatment failure after 6 months of therapy. Two patients had inducible, polymorphous VT that degenerated into ventricular fibrillation that required 2 countershocks before the successful restoration of sinus rhythm. One of these patients had VT stimulation by atrial pacing at a cycle length of 320 ms in the postflecainide electrophysiologic study. VT was not inducible by atrial pacing during this patient's preflecainide study.Thus, sustained oral flecainide administration may precipitate serious electrical instability in susceptible patients, and ventricular stimulation studies and other clinical variables may be useful in selecting patients with recurrent VT who may benefit or may be endangered by oral flecainide therapy.     

Management of refractory sustained ventricular tachycardia with amiodarone: a reappraisal

We examined the value of clinical variables, chronic 24-hour ambulatory ECG monitoring, and chronic electrophysiologic (EP) testing in 49 patients with recurrent and refractory sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) treated with chronic oral amiodarone in order to develop a prospective approach to the management of these patients. All patients underwent control EP studies followed by continuous telemetric cardiac monitoring during oral amiodarone administration (mean duration 29 +/- 6 days, mean dose 739 +/- 230 mg). Follow-up 24-hour ambulatory ECG monitoring and EP studies were performed. Thirty VT recurrences occurred in the first 4 weeks of amiodarone therapy (total incidence, 61%), with the majority (55%) in the first 3 weeks of treatment. During long-term follow-up (1 to 42, mean 15 +/- 12 months), there were 12 symptomatic VT/VF recurrences (incidence 24%). There was a higher incidence of VT recurrences if patients had inducible sustained or nonsustained VT at chronic EP study (p less than 0.01), or complex ventricular arrhythmias on ambulatory ECG monitoring (p less than 0.05). The sensitivity, specificity, and predictive accuracy of chronic EP testing and 24-hour ambulatory ECG monitoring were 100%, 35%, and 51%, and 58%, 84%, and 78%, respectively. Chronic EP testing correctly identified all patients who had their arrhythmia suppressed by amiodarone on long-term follow-up, while 42% of all VT recurrences occurred in patients without complex ventricular arrhythmias on 24-hour ambulatory ECG monitor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Clinical efficacy and electropharmacology of continuous intravenous amiodarone infusion and chronic oral amiodarone in refractory ventricular tachycardia

The clinical efficacy and electropharmacologic effects of continuous intravenous (i.v.) amiodarone infusion (10 to 20 mg/kg/day for 4 to 7 days) followed by chronic oral amiodarone therapy (400 to 800 mg/day for 24 to 53 days) were evaluated in 17 patients with refractory sustained ventricular tachycardia (VT) or ventricular fibrillation. Intravenous amiodarone infusion prolonged the RR interval (from 754 +/- 85 to 860 +/- 157 ms, p less than 0.05), PR interval (from 192 +/- 53 to 212 +/- 54 ms, p less than 0.01) QRS duration (from 103 +/- 21 to 117 +/- 25 ms, p less than 0.001) and QTc interval (from 423 +/- 22 to 466 +/- 31 ms, p less than 0.001). Chronic oral amiodarone treatment had similar but more pronounced effects on electrocardiographic intervals. The ventricular effective refractory period tended to prolong after i.v. amiodarone infusion (p less than 0.1 to greater than 0.05) but prolonged significantly after chronic oral amiodarone (p = 0.025). Mean serum amiodarone concentration was 1.7 +/- 1.0 mg/liter with infusion and 1.5 +/- 0.6 mg/liter with oral therapy. Intravenous amiodarone infusion suppressed spontaneous VT in 5 of 9 patients with frequent VT recurrences, but had no effect on cycle length of spontaneous VT. Chronic amiodarone therapy either suppressed spontaneous VT recurrences or prolonged cycle length during VT recurrences. VT induction after i.v. amiodarone was not predictive of VT induction or spontaneous VT recurrences after chronic oral amiodarone treatment. Thus, i.v. amiodarone has limited value in acute control of VT and clinical or electrophysiologic response to it is not predictive of long term therapeutic results with amiodarone.     

Chronic effects of amiodarone in patients with refractory ventricular tachycardia

We examined the chronic electrophysiologic, systemic, and pharmacologic effects of chronic oral amiodarone therapy in 24 patients with refractory ventricular tachycardia and organic heart disease. Chronic amiodarone therapy resulted in significant increases in R-R interval (from 798 +/- 182 msec to 912 +/- 100 msec; P less than 0.01), P-R interval (from 205 +/- 66 msec to 221 +/- 87 msec; P less than 0.02), QRS duration (from 103 +/- 24 msec to 115 +/- 28 msec; P less than 0.001), and Q-Tc interval (from 413 +/- 48 msec to 470 +/- 46 msec; P less than 0.001). Significant increases were also noted in P-A interval (from 36 +/- 14 msec to 45 +/- 13 msec; P less than 0.05), A-H interval (from 119 +/- 61 msec to 141 +/- 87 msec; P less than 0.02), and H-V interval (from 52 +/- 12 msec to 64 +/- 11 msec; P less than 0.001). Electrophysiologic parameters showing changes included corrected sinus node recovery time (from 271 +/- 140 msec to 425 +/- 122 msec; P less than 0.01), the effective refractory period of the atrium (from 263 +/- 32 msec to 321 +/- 47 msec; P less than 0.01), the effective refractory period of the atrioventricular node (from 348 +/- 109 msec to 478 +/- 157 msec; P less than 0.001), the effective refractory period of the ventricle (from 253 +/- 21 msec to 291 +/- 28 msec; P less than 0.001), the atrial pacing cycle length producing A-V nodal Wenckebach (from 436 +/- 109 msec to 531 +/- 95 msec; P less than 0.001), and the functional refractory period of the A-V node (from 422 +/- 68 msec to 499 +/- 95 msec; P less than 0.001). Programmed electrical stimulation performed after 21-88 (mean 31) days of treatment was highly predictive of long-term results if suppression of arrhythmia induction was demonstrated (12 patients) or if the spontaneous arrhythmia was reinduced (5 patients). Induction of morphologically new ventricular tachyarrhythmias was frequent (42%) but had a low spontaneous recurrence rate (10%) during follow-up. Systemic parameters on chronic amiodarone therapy showed significant increases in total T4 and reverse T3, with no change in pulmonary function tests or left ventricular ejection fraction. Serum amiodarone levels at chronic electrophysiologic study ranged from 0.44-4.10 (mean 1.3) micrograms/ml. Long-term follow-up (2.5 to 20 months) demonstrated a marked improvement in clinical symptoms and mortality, but a significant recurrence rate of a well-tolerated slower arrhythmia persisted. Adverse effects on chronic amiodarone therapy were frequent (10 patients) and often disabling but required drug discontinuation in only 1 patient.     

Propafenone treatment of recurrent ventricular tachycardia: comparison of continuous electrocardiographic recording and electrophysiologic study in predicting drug efficacy

Propafenone was administered to 29 patients who had multiple episodes of recurrent ventricular tachycardia (VT) or ventricular fibrillation (VF) despite previous antiarrhythmic therapy. All patients had 24-hour continuous electrocardiographic recording and electrophysiologic study in a drug-free control state and while receiving maximum doses of propafenone. During propafenone treatment, the mean frequency of ventricular premature complexes (VPCs) decreased 74% (p less than 0.05). There was more than an 83% decrease in VPC frequency in 17 of 29 patients, and 11 patients had 99 to 100% decreases. Propafenone prevented VT induction at electrophysiologic study in 6 patients, whereas another 12 patients were judged to have satisfactory electrophysiologic responses on the basis of slower VT rates and absence of hemodynamic compromise during VT. After long-term treatment from 2 to 26 months, 9 patients continued propafenone without evidence of recurrent arrhythmia. Six of these 9 patients had not VT induction at electrophysiologic study while receiving propafenone. The decrease in VPC frequency produced by propafenone was a poor predictor of a successful electrophysiologic study and of long-term therapy. In conclusion, propafenone has potential as an effective antiarrhythmic agent, but better methods to stratify risk for recurrence of VT and VF are needed.     

Electrophysiologic effects of ethmozin in patients with ventricular tachycardia

Ten patients with recurrent episodes of ventricular tachycardia (VT) had electrophysiologic studies in the basal state and on chronic oral ethmozin (12.1 ± 0.6 SE mg/kg/day). Ethmozin significantly prolonged the AH interval (basal: 75 ± 8 SE msec; ethmozin: 91 ± 10 msec, p < 0.05), the HV interval (51 ± 3; 66 ± 5 msec, p < 0.01), and the QRS duration (101 ± 4; 118 ± 4 msec, p < 0.001). Atrial and ventricular refractory periods and the corrected QT interval were not significantly affected by ethmozin. VT was induced in 7 of 10 patients in the basal state by means of programmed right ventricular extrastimulation or rapid burst ventricular pacing. On oral ethmozin nine patients had inducible VT. VT cycle length was consistently prolonged on ethmozin (250 ± 13; 326 ± 14 msec, p < 0.001). Four of the seven patients with VT on basal ambulatory monitoring had total abolition of spontaneous VT on ethmozin. Ethmozin failed to prevent induction of VT in most patients despite significant reductions in ventricular arrhythmia on ambulatory monitoring. Further studies comparing VT induction with ambulatory monitoring in patients on ethmozin are needed to confirm these findings and to define the clinical significance of this dissociation.     

Usefulness of electrophysiologic testing in evaluation of amiodarone therapy for sustained ventricular tachyarrhythmias associated with coronary heart disease

The prognostic importance of electrophysiologic studies in patients with sustained ventricular tachyarrhythmias treated with amiodarone was prospectively studied in 100 consecutive patients. Sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) was inducible in all patients before amiodarone therapy. After amiodarone administration 2 groups of patients were identified. In group 1 patients the ventricular tachyarrhythmia was no longer inducible and in group 2 patients the arrhythmia remained inducible. In group 1, no recurrent arrhythmia occurred during a follow-up of 18 +/- 10 months. In group 2, 38 of 80 patients (48%) had arrhythmia recurrence during a follow-up of 12 +/- 9 months. The difference between group 1 and 2 could not be explained by clinical variables, amiodarone doses or plasma concentrations, or electrocardiographic variables. In patients in whom cardiovascular collapse or other severe symptoms where noted during electrophysiologic study after amiodarone treatment, recurrences caused sudden death (n = 12). However, in patients in whom the induced arrhythmia produced moderate symptoms, the recurrent arrhythmia was nonfatal VT (n = 26). Electrophysiologic testing provides clinical guidance and predicts prognosis in patients treated with amiodarone as it does for the evaluation of other antiarrhythmic agents.     

Long-term efficacy and toxicity of high-dose amiodarone therapy for ventricular tachycardia or ventricular fibrillation

Amiodarone was administered to 154 patients who had sustained, symptomatic ventricular tachycardia (VT) (n = 118) or a cardiac arrest (n = 36) and who were refractory to conventional antiarrhythmic drugs. The loading dose was 800 mg/day for 6 weeks and the maintenance dose was 600 mg/day. Sixty-nine percent of patients continued treatment with amiodarone and had no recurrence of symptomatic VT or ventricular fibrillation (VF) over a follow-up of 6 to 52 months (mean ± standard deviation 14.2 ± 8.2). Six percent of the patients had a nonfatal recurrence of VT and were successfully managed by continuing amiodarone at a higher dose or by the addition of a conventional antiarrhythmic drug. One or more adverse drug reactions occurred in 51% of patients. Adverse effects forced a reduction in the dose of amiodarone in 41 % and discontinuation of amiodarone in 10% of patients. The most common symptomatic adverse reactions were tremor or ataxia (35 %), nausea and anorexia (8%), visual halos or blurring (6%), thyroid function abnormalities (6%) and pulmonary interstitial infiltrates (5%).Although large-dose amiodarone is highly effective in the long-term treatment of VT or VF refractory to conventional antiarrhythmic drugs, it causes significant toxicity in approximately 50% of patients. However, when the dose is adjusted based on clinical response or the development of adverse effects, 75 % of patients with VT or VF can be successfully managed with amiodarone.     

Ethmozine (moricizine HCl) therapy for complex ventricular arrhythmias

Moricizine HCl (Ethmozine), a new antiarrhythmic agent, was administered to 102 patients with refractory ventricular fibrillation (n = 31), sustained ventricular tachycardia (VT) (n = 46) or symptomatic nonsustained VT (n = 25). A noninvasive approach utilizing monitoring and exercise testing was used in 82 patients who had a high density of reproducible spontaneous arrhythmia, whereas 20 patients without such arrhythmia required invasive electrophysiologic testing. The dosage of moricizine HCl was 200 mg 3 times daily, and during 5 to 6 days was titrated up to a maximum of 400 mg 3 times daily or 15 mg/kg daily, based on arrhythmia suppression and occurrence of side effects. Criteria for efficacy were a greater than 90% reduction in repetitive ventricular premature beats (couplets and runs of VT) and a greater than 50% reduction in ventricular premature beats when noninvasive methods were used. When electrophysiologic testing was used, the drug was judged effective if it prevented the induction of greater than 2 repetitive responses. Of 75 patients completing noninvasive study, 30 (40%) responded to moricizine HCl therapy, whereas only 1 of 20 patients undergoing electrophysiologic testing responded. There was no difference in moricizine HCl blood levels between responders and nonresponders (0.41 microgram/ml vs 0.43 microgram/ml, difference not significant). Side effects occurred in 28 patients (27%). Most frequent were aggravation of arrhythmia (n = 12), nausea and vomiting (n = 5), central nervous system toxicity (n = 3) and anticholinergic side effects (n = 3). The response rate to moricizine HCl therapy was higher in patients with nonsustained VT (62%) compared with those with sustained VT (19%) or ventricular fibrillation (33%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Predictors of efficacy of amiodarone and characteristics of recurrence of arrhythmia in patients with sustained ventricular tachycardia and coronary artery disease

The value of serial electropharmacologic testing during long-term oral amiodarone therapy for prediction of long-term drug efficacy as well as characteristics of arrhythmia recurrence is controversial. One-hundred four consecutive patients with coronary artery disease and sustained ventricular tachyarrhythmias (VT) underwent initial electrophysiologic (EP) evaluation in the drug-free state and again after an amiodarone loading period of 25 +/- 14 days (mean +/- SD). Twenty-six patients (25%) had no inducible ventricular tachyarrhythmia during therapy with amiodarone (VT control group), whereas arrhythmia inducibility persisted in the remaining 78 patients (VT noncontrol group). During 17.4 +/- 13.7 months of follow-up, two patients in the VT control group either had VT recurrence or died suddenly compared with 21 VT recurrences and eight sudden cardiac deaths in the VT noncontrol group (actuarial event rates at 36 months of 0.11 and 0.56, respectively, p = .0065). The cycle lengths of recurrent VT in these 21 patients in the VT noncontrol group were compared with those observed at final EP testing. A significant linear correlation was demonstrated (r = .76, p = .0001). Subgroup analysis of patients in the VT noncontrol group showed no EP predictors of outcome, including cycle length of induced VT. However, patients dying suddenly during the follow-up period had a higher prevalence of new or worsening congestive heart failure (75%) compared with patients with VT recurrence (19%) or those with no arrhythmic event (29%) (p less than .02).2off     

Efficacy and tolerance of high-dose intravenous amiodarone for recurrent, refractory ventricular tachycardia

High-dose intravenous amiodarone was given to 35 patients with recurrent life-threatening ventricular tachycardia (VT) refractory to conventional antiarrhythmic agents. Intravenous amiodarone was given as a 5 mg/kg dose over 30 minutes followed by 20 to 30 mg/kg/day as a constant infusion for 5 days. Twenty-two (63%) patients responded to intravenous amiodarone. All 22 responders received oral amiodarone. Thirteen (59%) continue to receive oral amiodarone after an average follow-up of 19 months, 4 (18%) had sudden cardiac death on oral amiodarone, 2 (9%) died while receiving amiodarone, secondary to left ventricular failure, and 3 (14%) discontinued amiodarone because of side effects. Of the 13 (37%) nonresponders, 10 died in the hospital while receiving intravenous amiodarone, secondary to lethal arrhythmia. Three nonresponders were discharged from the hospital; 2 with automatic cardioverter/defibrillators and 1 receiving a combination of antiarrhythmic agents. Serious adverse events occurred in 13 (37%) patients during intravenous amiodarone therapy. These included hypotension in 8 patients, symptomatic bradycardia in 4 patients and sinus arrest with bradycardia and hypotension in 1 patient. Minor side effects occurred in 23 (66%) patients. In conclusion, high dose intravenous amiodarone is effective in most patients with recurrent, sustained VT but is associated with an unacceptably high incidence of serious adverse events. The optimal dose and duration of intravenous amiodarone for patients with recurrent, refractory sustained VT remain unknown.     

Value of a serial electropharmacologic study in survivors of a cardiac arrest secondary to ventricular tachycardia or ventricular fibrillation

Electrophysiologic studies were performed in 10 patients (8 M, 2 F, mean age: 60.2 yrs) who had survived an episode of cardiac arrest due to ventricular tachycardia (VT) or ventricular fibrillation. The purpose was to evaluate the usefulness of serial acute drug testing in selecting an effective chronic antiarrhythmic regimen. The cardiac arrest had always been sudden and unexpected. It occurred outside the hospital in 7 cases and in the hospital in 3 cases. Patients in whom cardiac arrest was associated with evidence of acute myocardial infarction were excluded from the study. Nine of the patients were suffering from chronic ischemic heart disease with 1 or more previous myocardial infarctions while 1 had no evidence of organic heart disease. A ventricular aneurysm was present in 4 of them. During control electrophysiologic study a sustained VT was induced by ventricular stimulation (single and double extrastimuli at various paced ventricular cycle lengths + bursts of rapid ventricular pacing) in 9 of the 10 patients (90%) and a non sustained VT was induced in 1 of them (10%). In 3 patients (30%) VT could be initiated only by right ventricular stimulation at a site different from the apex (outflow tract). During serial acute drug testing a totally effective drug regimen (successful in preventing the induction of any ventricular arrhythmia) was found in 6 of the 9 patients (66.7%) who underwent this procedure and a partially effective drug regimen (sustained VT no longer inducible, easier to interrupt and considerably slower) was found in 2 patients (22.2%). None of the patients who received a chronic antiarrhythmic therapy based on the results of serial acute drug testing died suddenly during a mean follow-up of 14.8 months (range: 3-29) and only 1 had a recurrence of cardiac arrest. The latter, however, was taking antiarrhythmic drugs at a dosage less than that proved to be effective during electropharmacological testing. The only patient who refused serial acute drug testing and received an empiric antiarrhythmic therapy died suddenly at the 21st month of the follow-up. It is also noteworthy that amiodarone, alone or in combination, was given chronically to 6 of our patients (60%). These results 1) indicate that serial electropharmacological testing is useful in selecting an effective long-term drug regimen in survivors of cardiac arrest, and 2) suggest that amiodarone may be effective in preventing sudden death in these patients.     

Usefulness of an implantable antitachycardia pacemaker system for supraventricular or ventricular tachycardia

The Cordis Omni-Orthocor model 234A, an implantable antitachycardia system, was evaluated in 13 patients. Two patients had recurrent sustained supraventricular tachycardia (SVT) and 11 had ventricular tachycardia (VT). The system was used for SVT or VT termination (group 1: SVT, 2 patients; VT, 4 patients) or for demand pacing and noninvasive electrophysiologic studies for tachycardia induction and serial electrophysiologic testing alone (group 2: VT, 7 patients). The overdriver was used successfully in 4 of 6 patients in group 1 for repeated tachycardia termination (SVT and VT) during a mean follow-up period of 18 months. One patient had 1 sustained VT episode unresponsive to pacing and 1 patient had no recurrence of tachycardia. Tachycardia termination zones varied when using the system in 2 patients receiving long-term amiodarone therapy. Eighteen noninvasive electrophysiologic studies for serial drug testing were performed, 4 in group 1 and 14 in group 2. Clinical tachycardia was induced and successfully terminated by use of the overdriver in 12 studies. It is concluded that implantable antitachycardia systems can be used successfully for noninvasive tachycardia induction and termination and for reliable serial electrophysiologic studies. Such systems provide improved patient safety and acceptability and are reasonable in cost.     

Effects of intravenous amiodarone in patients with inducible repetitive ventricular responses and ventricular tachycardia

We studied the effects of intravenous amiodarone administration (5 mg/kg) on reproducible repetitive ventricular responses and ventricular tachycardia (VT) induced by programmed electrical stimulation of the heart in 32 patients. Intravenous amiodarone prevented induction of bundle branch reentry in only 2 of 11 patients (18.2%) and did not change His-Purkinje conduction and refractoriness in the remaining 9 of 11 (81.8%) patients. In contrast to the small effect of intravenous amiodarone on bundle branch reentry, the drug completely abolished intraventricular reentry in three of nine (33.3%) patients and in the remaining six of nine (66.7%) patients decreased the number of intraventricular reentrant beats from up to five beats in control to one to two beats after the drug. The drug also prevented induction of VT (greater than or equal to 5 ventricular ectopic beats in a row) in three of five (60%) patients with nonsustained VT and in three of seven (42.9%) patients with sustained VT. In two of seven (28.6%) patients with sustained VT, only nonsustained tachycardia could be induced after drug administration. In another two of seven (28.6%) patients, sustained VT with slower rates was induced after the drug. In 11 of 12 (91.7%) patients with VT the coupling interval between the last stimulus and the first ventricular beat increased after drug administration. These effects of intravenous amiodarone occurred in the absence of effect on ventricular effective refractory period. These findings suggest that intravenous amiodarone might have greater effect on diseased ventricular tissue, the site of reentry in VT, than on healthy ventricular tissue.     

Electrophysiology of Ethmozine (moricizine HCl) for ventricular tachycardia

Moricizine HCl, an antiarrhythmic phenothiazine drug, was investigated for its efficacy against ventricular tachycardia (VT) in a group of 60 patients from 8 institutions using electrophysiologic testing before and after oral administration. Moricizine HCl significantly prolonged PR, QRS, AH and HV intervals and cycle length for atrioventricular nodal block, but had minimal or no effect on repolarization or cardiac refractory periods. Induction of sustained VT (in 33 patients) and nonsustained VT (in 14 patients) occurred at baseline. During moricizine HCl therapy, sustained VT was induced in 31 patients and nonsustained VT in 7 patients. In individual patients, suppression of VT induction was obtained in 18% of patients with sustained VT and in 27% of patients with nonsustained VT. Cycle length of induced VT was significantly prolonged by moricizine HCl therapy. During prospective follow-up of 37 patients, electrophysiologic study predicted recurrence of nonrecurrence of VT with a sensitivity value of 82% and specificity of 65%.     

Comparison of noninvasive arrhythmia induction techniques with electrophysiologic studies and evaluation of lorcainide in patients with symptomatic ventricular tachycardia

Twenty-six patients (19 men and 7 women) with symptomatic ventricular tachycardia (VT) were studied using invasive and noninvasive techniques to induce VT. Of the study population, 12% had syncope and VT on Holter monitoring, 30% had cardiac arrest and 58% had symptomatic VT. All patients had antiarrhythmic agents stopped 5 half-lives before evaluation and then had autonomic profile (upright tilt, cold pressor test, exercise testing and hand grip) as well as programmed electrical stimulation studies performed. Autonomic profile testing induced VT in 5 of 26 patients (19%) and in only 1 patient was the arrhythmia reproducibly induced. All 26 patients had VT induced on electrophysiologic testing; 9 patients had nonsustained and 17 had sustained VT. Lorcainide administered intravenously prevented VT induction in 20 of 26 patients tested, whereas procainamide was effective in 11 of 24 patients. Ten of the 13 not protected by procainamide were protected by lorcainide. Twenty patients were started on long-term lorcainide therapy and followed up for 29 +/- 3.4 months. Five patients have discontinued therapy, 2 because of breakthrough arrhythmias, 2 because of severe sleep-wake disturbances and 1 because of private physician preference. An additional 3 patients died during therapy because of myocardial infarction in 1, progressive myopathy in 1 and sudden death in 1. Sixty percent of patients started on lorcainide therapy have continued. In this patient population, noninvasive induction of VT is not a sensitive or reproducible technique in assessing antiarrhythmic therapy. Furthermore, when selected on the basis of electrophysiologic testing, lorcainide is a well-tolerated and effective antiarrhythmic agent.     

Requirements of non-pharmacologic interventions in the treatment of recurrent sustained ventricular tachycardia

Sixty-five patients (pts) with sustained ventricular tachycardia (VT) and 1 patient with symptomatic nonsustained VT were included in this study. Of these, 5 had died before electrophysiologic study (EPS) or determination of effective antiarrhythmic drugs. Inducibility of VT by our protocol varied from 69 to 100% according to underlying diseases. Drug efficacy was evaluated by using conventional drugs in all and using flecainide and amiodarone in some. However, more than 50% of pts with inducible VT were found to be resistant to pharmacological therapy. Fourteen of 26 pts with drug-refractory VT, underwent surgical therapy. In all pts, the site of VT origin was determined and VT was either eradicated or clinically controlled in 86% of the patients. Catheter ablation was tried in 9 pts at the earliest activation site of VT or at the site where pace-mapping produced the best result in configuration in the QRS complex as the clinical VT. Prophylactic effect was confirmed in 60% but VT recurred in 3 pts. These VT became responsive to anti-arrhythmic drugs in 2 pts. In thirteen pts who died suddenly during the follow up period, none had adequate antiarrhythmic drugs. One patient died after operation because of residual VT among four different QRS morphologies found preoperatively. In conclusion, the success rate antiarrhythmic drug prophylaxis against VT induction or recurrence did not exceed 50%, therefore non-pharmacological interventions such as surgery or catheter ablation may be required.