Efficacy and risks of moricizine in inducible sustained ventricular tachycardia.

OBJECTIVE: To assess the efficacy and toxicity of moricizine in treating patients with serious ventricular arrhythmias and inducible sustained ventricular tachycardia. DESIGN: Uncontrolled clinical trial. SETTING: The intensive care and telemetry units of Northwestern Memorial Hospital, St. Francis Hospital and Medical Center, and Lenox Hill Hospital. PATIENTS: Twenty-six patients with sustained ventricular arrhythmias or hemodynamically significant nonsustained ventricular tachycardia, most of whom failed therapy with at least one class I antiarrhythmic agent. INTERVENTION: Patients were treated with moricizine, 400 to 1000 mg/d. MEASUREMENT: Efficacy was assessed by the results of programmed ventricular stimulation done during moricizine therapy. MAIN RESULTS: Seven of the 26 patients (27%) developed life-threatening ventricular proarrhythmia during moricizine loading. Three patients had incessant sustained ventricular tachycardia, two had incessant nonsustained ventricular tachycardia, one had new sustained ventricular tachycardia, and one had new cardiac arrest. One of these patients died of intractable ventricular fibrillation. No clinical or electrophysiologic variables clearly identified those at risk for proarrhythmia. Only 3 of 26 patients (12%) became noninducible on moricizine. CONCLUSION: Moricizine has a low rate of efficacy and carries a considerable risk for life-threatening proarrhythmia in patients with serious ventricular arrhythmias and inducible ventricular tachycardia who have failed therapy with other class I antiarrhythmic agents.     

Proarrhythmic effects of antiarrhythmic drugs during programmed ventricular stimulation in patients without ventricular tachycardia

The proarrhythmic effects of class IA antiarrhythmic drugs were prospectively evaluated during programmed ventricular stimulation in 24 consecutive patients with frequent ventricular premature beats whose baseline study, performed while no antiarrhythmic drugs were being taken, showed no inducible sustained ventricular arrhythmias. No patient had nonsustained (greater than 5 beats) or sustained ventricular tachycardia by history or baseline 24 hour ambulatory electrocardiographic monitoring. Sequential stimulation studies using up to three extra-stimuli were performed after administration of procainamide, quinidine and disopyramide on different days. Proarrhythmic response was defined as induction of one or more of the following: sustained monomorphic ventricular tachycardia; sustained polymorphic ventricular tachycardia; ventricular fibrillation; reproducibly inducible nonsustained monomorphic ventricular tachycardia. During 55 antiarrhythmic drug trials (24 of procainamide, 21 of quinidine, 10 of disopyramide) in the 24 patients, 6 patients had a proarrhythmic response: sustained monomorphic ventricular tachycardia in 3, ventricular fibrillation in 2, nonsustained monomorphic ventricular tachycardia in 1. Thus, 11% of drug trials resulted in a proarrhythmic response and 25% of patients had a proarrhythmic response to one of the drugs tested. A proarrhythmic response to one drug did not predict a similar response to another drug of the same class. The 6 patients with a proarrhythmic response did not differ significantly from the other 18 patients with regard to underlying heart disease, electrocardiographic or baseline 24 hour ambulatory electrocardiographic characteristics; however, they did have a higher incidence of digoxin usage (p less than 0.02), a shorter baseline right ventricular effective refractory period (p less than 0.01) and a smaller increment in effective refractory period during antiarrhythmic drug testing (p = 0.06).(ABSTRACT TRUNCATED AT 250 WORDS)     

Reversal of proarrhythmic effects of flecainide acetate and encainide hydrochloride by propranolol

The use of membrane-active antiarrhythmic agents may be complicated by aggravation of existing arrhythmias or development of new drug-induced arrhythmias. Four patients, referred because of out-of-hospital cardiac arrest or symptomatic sustained ventricular tachycardia, were receiving class IC antiarrhythmic agents in an attempt to prevent inducibility of sustained ventricular tachycardia. New or worsening spontaneous arrhythmias developed while they were on flecainide acetate (n = 3) or encainide hydrochloride (n = 1) therapy. Spontaneous runs of rapid nonsustained and sustained ventricular tachycardia developed in two. Increased frequency of premature ventricular contractions and repetitive forms of ventricular ectopic activity developed in one, despite the fact that inducibility of sustained ventricular tachycardia had been prevented. Salvos and nonsustained ventricular tachycardia developed in the fourth patient. Propranolol had failed to prevent inducibility of sustained ventricular tachycardia during previous programmed stimulation studies in three of the four patients, but it reproducibly suppressed drug-induced arrhythmias that appeared only after administration of the IC agents in each patient. Suppression of the proarrhythmic effects by beta-adrenergic blockade suggests a possible interaction of these drugs with autonomic function in the genesis of the observed proarrhythmic effects. Direct pharmacologic control of proarrhythmic drug effects has not previously been reported.     

Clinical types of proarrhythmic response to antiarrhythmic drugs

The problem of drug-induced or drug-aggravated cardiac arrhythmias has been recognized for many years. Digitalis glycosides and class I, II, III, or IV antiarrhythmic drugs can cause severe sinus node dysfunction or atrioventricular block. Digitalis can cause a variety of supraventricular arrhythmias; atrial tachycardia with block and nonparoxysmal atrioventricular junctional tachycardia are the most characteristic. Recognition that class IA and class III antiarrhythmic drugs can aggravate arrhythmias or cause new arrhythmias in patients being treated for potentially malignant or malignant ventricular arrhythmias has intensified the interest in proarrhythmia in recent years. Several characteristic types of proarrhythmic response have been described. Torsades de pointes (multiform) ventricular tachycardia (VT) accompanied by prolongation of the QT interval can be caused by class IA and class III antiarrhythmic drugs as well as other drugs that bind to the membrane sodium channels of ventricular cells, for example, tricyclic antidepressants. Uniform VT in patients with malignant ventricular arrhythmias and poor left ventricular function is a characteristic proarrhythmic response to class IC antiarrhythmic drugs. Bidirectional VT or accelerated idioventricular rhythm are characteristic of digitalis toxicity. More difficult to establish as proarrhythmic responses are increased frequency of ventricular premature depolarizations and increased ease of inducing VT with programmed ventricular stimulation.     

Antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with coronary artery disease as assessed by electrophysiologic studies

The efficacy and proarrhythmic potential of antiarrhythmic agents were evaluated. Programmed ventricular stimulation was performed in 160 consecutive patients with coronary artery disease during a baseline study and 432 subsequent drug studies. The tachyarrhythmlas induced during baseline studies were sustained ventricular tachycardia (121 patients), ventricular fibrillation (16 patients), and symptomatic nonsustained ventricular tachycardia (23 patients). Regimens were completely successful if fewer than 6 repetitive ventricular responses were inducible during therapy and partially successful if no more than 15 repetitive ventricular responses were inducible. Procainamide and quinidine were the most successful single agents, with overall success rates of 24% and 35%, respectively. Either procainamide or quinidine combined with mexiletine was the most successful combination (overall success of 23% ). Each antiarrhythmic regimen showed a proarrhythmic potential. The incidence of proarrhythmic effects ranged from 4 to 13%, with no significant difference between regimens. In 13% of patients at least 1 regimen produced a proarrhythmic effect. Patients treated with an antiarrhythmic regimen that prevented induction of arrhythmia had significantly fewer arrhythmia recurrences than patients treated with a regimen that failed to prevent it. In conclusion, identification of an effective drug regimen is possible in 38% of patients with lethal ventricular arrhythmias, proarrhythmic effects occur in a significant number of patients during electrophysiologic testing of antiarrhythmic regimens, and the clinical outcome in patients in whom ventricular arrhythmias are not inducible with ventricular stimulation have a better prognosis than those in whom arrhythmias continue to be inducible on therapy.     

Inefficacy and proarrhythmic effects of flecainide and encainide for sustained ventricular tachycardia and ventricular fibrillation

OBJECTIVE: To assess the efficacy of encainide and flecainide in treating patients with sustained ventricular arrhythmias. DESIGN: Patients were treated with encainide or flecainide. Efficacy was assessed by comparing the results of programmed ventricular stimulation while patients received therapy with the results while they were drug free. SETTING: The electrophysiology laboratory of the University of California at San Francisco. PATIENTS: Forty-nine patients with spontaneous or inducible sustained ventricular tachycardia or ventricular fibrillation for whom treatment with at least one class IA antiarrhythmic agent had failed. INTERVENTIONS: Patients were treated with encainide, 35 to 50 mg three or four times daily, or flecainide, 100 to 200 mg twice daily. RESULTS: Arrhythmia worsened early in 5 of 16 patients receiving encainide and 3 of 33 patients receiving flecainide. Patients with poor left ventricular function were more likely to exhibit proarrhythmia (P = 0.02). Nine of eleven patients receiving encainide and 23 of 28 patients receiving flecainide who had repeat programmed ventricular stimulation while receiving drug therapy still had inducible, poorly tolerated ventricular tachycardia. CONCLUSION: Encainide and flecainide have a low efficacy rate and a high incidence of worsening of arrhythmia in patients with sustained ventricular arrhythmias, particularly when this condition is associated with poor left ventricular function.     

Usefulness of the electrophysiology laboratory for evaluation of proarrhythmic drug response in coronary artery disease.

Two potential manifestations of proarrhythmic responses to type IA antiarrhythmic agents in the electrophysiology laboratory were evaluated in 122 patients with chronic coronary artery disease and previous myocardial infarction: (1) conversion of uniform nonsustained ventricular tachycardia (VT) into sustained VT after drug administration, and (2) induction of sustained VT by fewer extrastimuli after drug administration. Forty-two patients were evaluated for nonsustained VT. Eighty patients were evaluated for sustained VT: 30 of these had spontaneous sustained VT only while receiving empiric therapy with quinidine or procainamide, whereas the remaining 50 developed spontaneous VT in the absence of antiarrhythmic drugs. All patients underwent programmed stimulation in the baseline state and after procainamide. Four patients had conversion of induced uniform nonsustained VT into the same morphology, but sustained VT after procainamide administration. These responses only occurred in patients evaluated for nonsustained VT. Over 90% of patients presenting with sustained VT had uniform sustained VT induced at the baseline study and after procainamide, regardless of whether the spontaneous arrhythmia occurred only in the presence or absence of antiarrhythmic drugs. There was no significant difference in the change in mode of induction from baseline to procainamide study, regardless of whether patients had developed spontaneous VT only in the presence or absence of antiarrhythmic drugs. One patient with no inducible VT at the baseline study had inducible uniform sustained VT after procainamide administration, and 1 patient with inducible VT at baseline developed spontaneous sustained uniform VT after procainamide administration. Both patients had developed spontaneous sustained VT only while receiving therapy with type IA agents.(ABSTRACT TRUNCATED AT 250 WORDS)     

Spontaneous sustained ventricular tachyarrhythmias during treatment with type IA antiarrhythmic agents

Twenty-six patients who developed their first clinical episode of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) while taking type IA antiarrhythmic agents for more benign rhythm disturbances were rechallenged with the identical drug during electrophysiologic testing. Patients with these new drug-associated spontaneous ventricular arrhythmias often manifested a preexisting substrate for such arrhythmias: sustained VT or VF was induced in 65% of patients at baseline, and in 58% of patients when tested with their previously taken antiarrhythmic drug. Among those without inducible sustained ventricular arrhythmias in the drug-free state, 78% remained free of inducible sustained arrhythmias when tested with the same drug they had been taking at the time of the clinical arrhythmia. Even patients without a definable electrophysiologic substrate for sustained VT or VF remained at risk for arrhythmia recurrence if treated with alternative antiarrhythmic medications: 40% of such patients who continued to receive an antiarrhythmic agent different from that being administered when their clinical VT or VF occurred had recurrent spontaneous ventricular tachyarrhythmias during follow-up. Thus, patients with drug-associated clinical sustained ventricular tachycardias form a heterogenous group that should be evaluated individually and not empirically managed for a "proarrhythmic effect" simply by antiarrhythmic drug withdrawal or drug substitution.     

Proarrhythmic effects of the new antiarrhythmic agent flecainide acetate

Flecainide acetate, a new potent class I antiarrhythmic agent, was given to 152 patients (46 orally and 106 intravenously) over a period of 22 months. Seven patients developed proarrhythmic effects. The only conduction abnormalities induced were PR interval prolongation and QRS complex widening, and no patient developed significant sinus bradyarrhythmias; patients with known serious abnormalities of impulse generation or conduction were excluded from this study. Five patients developed ventricular tachycardia or ventricular fibrillation of whom only three had preexisting ventricular arrhythmias. QT and QT_c interval prolongation was observed but was due to QRS complex widening rather than to an increase in the JT interval. A patient with the Wolff-Parkinson-White syndrome had an inducible orthodromic atrioventricular (AV) tachycardia prior to flecainide, but only an antidromic tachycardia was induced after the drug. In one patient flecainide administration resulted in an increase of atrial flutter cycle length which resulted in development of 1:1 AV conduction and overall faster ventricular rate. Two patients who developed ventricular arrhythmias were taking other antiarrhythmic agents, and in this series proarrhythmic effects occurred with both normal and high flecainide concentrations.     

Predictors of inducible sustained ventricular tachyarrhythmias in patients with coronary artery disease

To determine predictors of inducible sustained ventricular tachycardia or fibrillation by programmed electrical stimulation in patients with coronary artery disease and ventricular tachyarrhythmias, 14 clinical and angiographic variables were analyzed in 60 consecutive patients. All patients had angiographically documented coronary artery disease and symptomatic ventricular arrhythmias (sustained ventricular tachycardia in 21, ventricular fibrillation in 21 and nonsustained ventricular tachycardia in 18). Baseline programmed electrical stimulation while the patient was not taking antiarrhythmic drugs was performed with use of single, double and triple extrastimuli and burst pacing from two right ventricular sites. The variables analyzed were presenting arrhythmia; presence, frequency and complexity of ventricular ectopic activity on baseline 24 h electrocardiographic (Holter) monitoring; greater than or equal to 70% narrowing in either the left anterior descending, proximal left anterior descending, right coronary or circumflex coronary artery (independently assessed); single, double or triple vessel coronary disease; anterior, apical or inferior wall motion abnormalities; segmental dyskinesia and ejection fraction. Thirty-seven patients (62%) had inducible sustained ventricular tachycardia (rate greater than 100 beats/min, duration greater than 30 s or requiring cardioversion) and two patients (3%) had ventricular fibrillation induced. Eleven patients (18%) had nonsustained ventricular tachycardia (duration greater than or equal to 3 beats, less than 30 s) induced and 10 patients (17%) had no inducible arrhythmia (duration less than 3 beats). Multivariate stepwise logistic regression analysis identified three independent variables predictive of inducible sustained ventricular arrhythmias: sustained ventricular tachycardia as the presenting arrhythmia (p = 0.004), proximal left anterior descending artery lesion (p = 0.002) and anterior wall motion abnormality (p = 0.005).(ABSTRACT TRUNCATED AT 250 WORDS)     

Efficacy and safety of moricizine in patients with congestive heart failure: a summary of the experience in the United States.

Patients with ventricular premature beats (VPBs) and congestive heart failure (CHF) have an increased risk of sudden death, yet suppression of arrhythmia in this population is frequently complicated by proarrhythmia and by the negative inotropic effects of antiarrhythmic drugs. The purpose of this study was to evaluate the safety and efficacy of moricizine in patients with clinical CHF. The New Drug Application data base submitted to the Food and Drug Administration was analyzed. A total of 908 patients were treated with moricizine for ventricular arrhythmias; CHF developed in 49 of them (5.4%). Of the 908 patients, 374 had a history of CHF, 326 of whom tolerated moricizine for a mean of 97 +/- 217 days. New-onset CHF occurred only once (1/546 = 0.2%). Recurrence or exacerbation of clinical CHF during treatment with moricizine occurred in 48 of 374 patients (12.8%), 28 of whom continued to take moricizine with alteration in CHF therapy. The mean left ventricular ejection fraction (LVEF) of those patients in whom CHF developed was 26%. It is important to note that patients with a history of CHF were as likely to have suppression of VPBs (defined as greater than or equal to 75% reduction) as those without a history of CHF. In fact, suppression of arrhythmia was achieved as often in patients with LVEF less than 30% as in those with more preserved LVEF. Of the 374 patients with a history of CHF, 15 (4%) had a proarrhythmic event within 14 days of therapy. The incidence of sudden cardiac death in this group was 0.8%. These proarrhythmia rates compare favorably with those of other antiarrhythmic drugs.(ABSTRACT TRUNCATED AT 250 WORDS)     

Electrophysiology and antiarrhythmic efficacy of intravenous pirmenol in patients with sustained ventricular tachyarrhythmias

We assessed the electrophysiologic effects and antiarrhythmic efficacy of intravenous pirmenol in 15 patients who had spontaneous and induced sustained ventricular tachyarrhythmias. At a plasma concentration of 2.29 +/- 0.75 micrograms/ml, pirmenol decreased sinus cycle length by 11 +/- 13%, increased QRS, QTc, and HV intervals by 14 +/- 12%, 13 +/- 12%, and 22 +/- 28%, respectively, and increased atrial and ventricular effective refractory periods (ERP) by 20 +/- 14% and 7 +/- 8%, respectively. There was a greater increase in QRS duration during ventricular tachycardia and ventricular pacing than during sinus rhythm (p less than 0.005). By electropharmacologic testing, pirmenol was judged effective in six patients (40%) and was proarrhythmic in one (6%). In the nine patients in whom pirmenol was judged ineffective, the cycle length of induced VT increased by 36 +/- 15% and the associated mean arterial pressure increased by 21 +/- 14 mm Hg. The only side effects were mild hypotension and mild nausea in one patient each. Intravenous pirmenol has type IA electrophysiologic effects. It can be administered safely to patients with sustained ventricular tachyarrhythmias and is as effective as approved antiarrhythmic drugs when assessed by electropharmacologic testing.     

Inhibitory effect of moricizine on reperfusion induced tachyarrhythmias in rats--a comparison study with disopyramide and mexiletine.

Acute ligation of proximal left coronary artery was performed on forty male Sprague-Dawley rats. Five min later, occlusion was released in order to evaluate the effectiveness of the 3 antiarrhythmic drugs in eliminating reperfusion ventricular arrhythmias. The drugs evaluated were moricizine (5 mg/kg), disopyramide (DSP) (5 mg/kg) and mexiletine (MXT) (5 mg/kg), which were administered intravenously 5 min before ligation of the coronary artery. Compared to control rats that underwent identical experimental procedures, all 3 drugs significantly lowered the mortality rate from 90% of the control group to 20, 20 and 0% for moricizine, DSP and MXT groups. The incidence of ventricular fibrillation (Vf) was also decreased significantly by these drugs. The duration of ventricular tachycardia (VT) and Vf of surviving rats in drug groups were 111.7 +/- 35.0 sec, 71.6 +/- 29.4 sec and 32.9 +/- 14.6 sec for moricizine, DSP and MXT, respectively. Many of the drug treated rats could be restored to the normal sinus rhythm and survived. All 3 drugs slowed the heart rate significantly, but as for the blood pressure only MXT showed significant suppressing effect. In conclusion, moricizine has the same significant preventive effect on reperfusion induced ventricular tachyarrhythmias as DSP and MXT.     

Activation mapping in patients with coronary artery disease with multiple ventricular tachycardia configurations: occurrence and therapeutic implications of widely separate apparent sites of origin

Catheter or intraoperative activation mapping studies, or both, were performed in 17 patients with coronary artery disease with two to four distinct configurations of ventricular tachycardia, resistant to a mean of 12.1 +/- 6.0 antiarrhythmic drug trials per patient. Mapping studies were performed to guide anticipated surgical ablation of arrhythmias. Activation map data were adequate to determine sites of origin of 30 (64%) of 47 observed tachycardia configurations. These 30 ventricular tachycardias (26 observed clinically) were mapped to 22 separate endocardial sites of origin. Sites of origin of distinct tachycardias were identical or closely adjacent (within 3 cm) in six patients and widely separate (greater than or equal to 4 cm) in eight patients (47% of the group). Activation maps were not adequate to determine sites of origin of 17 (36%) of the 47 tachycardias, including all configurations in three patients. Fifteen patients underwent surgery for control of ventricular tachycardia: aggressive, map-guided endocardial resection (mean 26.5 +/- 14.2 cm2) in 12 patients with identified sites of tachycardia origin and extensive resection of visible endocardial scar (2 patients) or encircling endocardial ventriculotomy (1 patient) in those in whom the sites of origin of all clinical tachycardias remained undetermined. Two inoperable patients were treated with amiodarone. During postoperative electrophysiologic tests (11 of 13 surgical survivors), ventricular tachyarrhythmias were initially uninducible in only 4 of 11 patients. However, in two patients only nonclinical arrhythmias (ventricular flutter) were induced. Six (21%) of 29 clinical tachycardias whose sites of origin were either not determined or not resected (right septum or papillary muscle) remained inducible in five patients. Using previously ineffective antiarrhythmic drugs, initially inducible arrhythmias became uninducible (two patients), or harder to induce than preoperatively (five patients). As a result of surgical resections alone or in combination with previously ineffective drugs (and amiodarone in two inoperable patients), there were no recurrences of ventricular tachycardia in 14 (93%) of 15 patients discharged during 19.0 +/- 14.3 months of follow-up study. Thus, activation mapping may commonly reveal separate apparent sites of origin for clinically observed, morphologically distinct, highly drug-refractory ventricular tachycardias in patients with coronary artery disease with multiple tachycardia configurations. Extensive surgical resection of identified sites of origin may be required to ablate arrhythmias in these patients.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reperfusion arrhythmias in acute myocardial infarction]

Twenty-seven patients with acute myocardial infarction (AMI), in whom infarct-related coronary artery was occluded and thrombolytic therapy or PTCA were performed, were studied. Reperfusion confirmed by immediate coronary angiography was achieved in 24 patients. Reperfusion arrhythmias (RA) occurred in 19(79.2%) of the patients, including ventricular arrhythmias in 13 (54.2%). Ventricular fibrillation (VF) and sustained ventricular tachycardia (VT) developed in 2(8.4%), and accelerated idioventricular rhythm in 5(20.8%); the latter showed a reliable indicator of coronary artery recanalization. Transient sinus bradycardia or AV block occurred in 10 (66.7%) of the 15 patients with inferior-posterior MI, which was an indicator of recanalization of coronary artery and salvage of myocardium in inferior-posterior MI. The occurrence of RA was not correlated with the duration of ischemia; ventricular RA was not related to the location of AMI and the occurrence and severity of ischemic arrhythmias before reperfusion. The patients with RA were treated with ordinary antiarrhythmic therapy, VF and sustained VT in 2 patients were converted by electric defibrillation. No death related to RA occurred. RA couldn't be prevented by lidocaine.     

Exacerbation of ventricular arrhythmias during the postoperative period after implantation of an automatic defibrillator

The postoperative course of 68 consecutive patients treated with an implantable defibrillator during the period from 1982 through 1990 was studied. In 46 patients (group 1), no concomitant surgery was performed during the implantation. In 22 patients (group 2), concomitant surgery (coronary artery bypass [n = 12], valve replacement [n = 3] or arrhythmia surgery [n = 7]) was performed. All patients in group 1 were clinically stable before surgery, receiving an antiarrhythmic regimen chosen by serial drug testings. The same regimen was continued postoperatively. Eight of the 46 patients in group 1 whose condition had been stable in the hospital for 19 +/- 25 days preoperatively developed multiple episodes of sustained ventricular tachycardia 4 +/- 9 days after implantation while receiving the same antiarrhythmic regimen. Although the exacerbation was transient in some patients, six required different antiarrhythmic therapy and one eventually died. Two additional patients had frequent and prolonged episodes of nonsustained ventricular tachycardia that could trigger the defibrillator, requiring changes in the antiarrhythmic regimen. Another patient had progressive cardiac failure and died on day 5. A marked (sevenfold) increase in asymptomatic ventricular arrhythmias was noted in 42% of the remaining 35 patients. In group 2 (combined surgery), one patient developed refractory ventricular tachycardia 3 days postoperatively and died on that day. Three patients developed frequent nonsustained ventricular tachycardia postoperatively, requiring changes in the antiarrhythmic regimen. The overall surgical mortality rate was 4.4% (4.3% in group 1 and 4.5% in group 2) and was due to refractory ventricular tachycardia in two patients and cardiac failure in one.(ABSTRACT TRUNCATED AT 250 WORDS)     

Long-term reproducibility and significance of provokable ventricular arrhythmias after myocardial infarction

The long-term reproducibility and significance of inducible ventricular arrhythmias were assessed in 21 survivors of a myocardial infarction. Programmed ventricular stimulation performed a mean of 12 +/- 2 days (range 8 to 18) after infarction provoked ventricular fibrillation in 2 patients, sustained monomorphic ventricular tachycardia in 8 and nonsustained ventricular tachycardia in 11. Patients were restudied using the same protocol a mean of 8 +/- 2 months (range 4 to 11) after infarction. All patients underwent programmed ventricular stimulation studies in the absence of antiarrhythmic drug treatment. Ventricular tachyarrhythmias could be reinitiated in 16 patients (76%): ventricular fibrillation in 2, sustained ventricular tachycardia in 5 (monomorphic in 4) and nonsustained ventricular tachycardia in 9. A preponderance of inferior infarction was observed among patients with reinducible tachycardias (9 of 16 patients versus 0 of 5 with noninducible tachycardias) (p less than 0.05). No significant difference existed between patients with and without reinducible arrhythmias with respect to severity of coronary artery disease, degree of left ventricular dysfunction, occurrence of ventricular fibrillation in the acute phase of infarction and ventricular arrhythmias detected by 24 hour ambulatory electrocardiographic (Holter) monitoring. There was no significant difference between patients with and without a positive late study in stimulation thresholds, ventricular refractory periods, time interval between initial and repeat testing and use of beta-adrenergic blocking agents. During a mean follow-up period of 17 months (range 10 to 23) one patient with inducible sustained monomorphic ventricular tachycardia at both studies died suddenly. The remaining patients have survived follow-up without experiencing an arrhythmic event.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ethmozine: electrophysiology, hemodynamics, and antiarrhythmic efficacy in patients with life-threatening ventricular arrhythmias

Thirteen patients with drug-resistant, life-threatening ventricular arrhythmias and inducible sustained ventricular tachycardia (VT) at electrophysiologic study received moricizine HC1 (ethmozine), 10 mg/kg/day orally. Eight patients underwent electrophysiologic study before and after drug administration; the arrhythmia became noninducible in one. In five other patients, spontaneous sustained VT occurred after 1 to 5 days of drug therapy, and one patient had a worsening of arrhythmias on ethmozine. Ethmozine prolonged infranodal conduction time (HV interval) (51.4 +/- 13.8 msec to 69.3 +/- 17.7 msec [mean +/- SD]), PR interval (201 +/- 28.1 msec to 244 +/- 62.2 msec), and QRS interval (123 +/- 27 msec to 147 +/- 32 msec). Ventricular refractory periods were not consistently affected, and only the one patient who became noninducible had an increase in effective ventricular refractory period (280 to 310 msec). The drug had no significant effect on sinus cycle length or sinus node recovery time, atrial conduction or refractoriness, or atrioventricular nodal refractoriness. Ethmozine had no effect on radionuclide ejection fraction (25.5 +/- 12.7% to 28.2 +/- 13.8%) or cardiac index (2.4 +/- 0.7 to 3.0 +/- 0.6 ml/min/m2) and caused no significant changes in mean aortic, right atrial, pulmonary arterial, or pulmonary capillary wedge pressures. Although the drug is well tolerated and produces no untoward hemodynamic effects, ethmozine is relatively ineffective in patients with sustained VT refractory to conventional antiarrhythmic agents.     

Effects of Ethmozine (moricizine HCl) on ventricular function using echocardiographic, hemodynamic and radionuclide assessments

Ventricular arrhythmias combined with left ventricular (LV) dysfunction in patients portend a poor prognosis. Most antiarrhythmic agents have not been sufficiently investigated to adequately describe detrimental effects on LV function; we report the effects of moricizine HCl on ventricular function in 4 trials highlighting patients with LV dysfunction. Quantitative 2-dimensional echocardiography was used to evaluate 81 patients pre- and posttreatment. There was no change in mean global LV ejection fraction (EF) during placebo compared with moricizine HCl therapy (47 +/- 15% vs 46 +/- 14%, p greater than 0.05). In a separate trial, radionuclide LVEF at rest and exercise tolerance testing were performed in 24 patients with life-threatening ventricular arrhythmias who had a mean control LVEF of 40 +/- 19%. No significant change during moricizine HCl therapy (38 +/- 19%, p greater than 0.05) was detected and exercise parameters were unchanged. Rest and exercise LV function was measured during right-sided heart catheterization in a placebo-controlled study of 20 patients with ventricular tachycardia. Moricizine HCl was well tolerated without hemodynamic deterioration in all but 3 patients, who could be identified by their inability to increase stroke volume index during exercise. Finally, the relation between initial LV function and resultant antiarrhythmic efficacy indicates that moricizine HCl controls arrhythmias best in patients with LVEF greater than 30%.     

Indications for and long-term survival in patients with automatic implantable cardioverter-defibrillators

Automatic implantable cardioverter-defibrillators (AICDs) were implanted in 378 men and 95 women, mean age 69 +/- 12 years. At 3.6-year follow up, survival was 76% in patients who had an AICD because of cardiac arrest as a result of ventricular fibrillation or ventricular tachycardia not resulting from a transient or reversible cause; 85% in patients who had an AICD because of spontaneous sustained ventricular tachycardia in association with structural heart disease; 92% in patients who had an AICD because of syncope of undetermined origin with clinically relevant, hemodynamically sustained ventricular tachycardia or ventricular fibrillation induced at electrophysiological study when drug therapy is ineffective, not tolerated, or not preferred; 84% in patients who had an AICD because of nonsustained ventricular tachycardia with coronary artery disease, prior myocardial infarction, left ventricular dysfunction, and inducible ventricular fibrillation or sustained ventricular tachycardia at electrophysiological study that is not suppressible by a class I antiarrhythmic drug; and 85% in all 473 patients who had an AICD.