Scott R. Spielman

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.

The NASPE*/BPEG** Generic Pacemaker Code for Antibradyarrhythmia and Adaptive‐Rate Pacing and Antitachyarrhythmia Devices

A new generic pacemaker code, derived from and compatible with the Revised ICHD Code, was proposed jointly by the North American Society of Pacing and Electrophysiology (NASPE) Mode Code Committee and the British Pacing and Electrophysiology Croup (BPEC), and has been adopted by the NASPE Board of Trustees. It is abbreviated as the NBC (for “NASPE/BPEC Generic”) Code, and was developed to permit extension of the generic‐code concept to pacemakers whose escape rate is continuously controlled by monitoring some physiologic variable, rather than determined by fixed escape intervals measured from stimuli or sensed depolarizations, and to antitachyarrhythmia devices including cardioverters and defibrillators. The NASPE/BPEC Code incorporates an “R” in the fourth position to signify rate modulation (adaptive‐rate pacing), and one of four letters in the fifth position to indicate the presence of antitachyarrhythmia‐pacing capability or of cardioversion or defibrillation functions.

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 tachyarrhythmias 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 anti-arrhythmic 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.

Efficacy of combination therapy with mexiletine and a type IA agent for inducible ventricular tachyarrhythmias secondary to coronary artery disease

The efficacy of combination therapy using a type IA agent (quinidine or procainamide) and a type IB agent (mexiletine) in suppressing inducible sustained ventricular tachyarrhythmias was studied in 23 patients undergoing serial drug testing with programmed stimulation. All patients had coronary artery disease (CAD) with previous myocardial infarction and abnormal left ventricular function (mean ejection fraction 35%). Fifty-five percent of the patients presented with syncope or cardiac arrest. In 19 patients therapy had failed during empiric trials of 1 to 3 antiarrhythmic agents. All 23 patients had inducible sustained ventricular tachyarrhythmias (18 had uniform morphology sustained ventricular tachycardia (VT) and 5 had ventricular fibrillation [VF]) during control electrophysiologic study, and therapy had failed with a type IA agent and mexiletine alone. The combination therapy of mexiletine and the type IA agent prevented induction of any ventricular tachyarrhythmias in 8 of 23 patients. In 15 patients, the combination significantly prolonged the tachycardia cycle length and reduced the symptoms associated with the induced arrhythmia. Patients more likely to respond to the combination had shorter cycle lengths and polymorphic configuration of the control-induced arrhythmia. The increased efficacy of the combination therapy could not be attributed to higher plasma drug levels for the combination, as there was no significant difference in plasma levels for each drug when given alone or in combination. Thus, the increased efficacy most likely reflects a synergistic electropharmacologic effect of the 2 agents.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrophysiologic assessment of antiarrhythmic drug efficacy for ventricular tachyarrhythmias associated with dilated cardiomyopathy.

To determine the benefit of serial electrophysiologic drug testing in patients with ventricular tachyarrhythmias related to dilated cardiomyopathy, programmed ventricular stimulation was performed in 38 patients. In the baseline study, sustained ventricular tachycardia (VT) was induced in 18 patients, ventricular fibrillation in 7 and nonsustained VT in 13. The patients underwent a total of 84 trials of drug therapy (mean 2.3 +/- 1.4 trials/patient). Complete success (induction of fewer than 6 repetitive responses) was recorded in 19 trials and partial success (induction of at least 6 but no more than 15 repetitive responses) in 7. Potential proarrhythmic effects were observed in 9 trials. Overall, at least 1 successful regimen was identified for 20 patients (53%). During a mean follow-up of 21 +/- 13 months, there were no arrhythmia recurrences or episodes of sudden death among patients discharged with a drug regimen determined to be effective by serial drug testing. In comparison, among patients taking regimens that failed to prevent arrhythmia induction, there were 3 arrhythmia recurrences and 2 sudden deaths (p less than 0.05). Serial electrophysiologic drug testing provides an effective method of identifying successful medical therapy for patients with ventricular arrhythmia related to dilated cardiomyopathy.

Proarrhythmic responses during electrophysiologic testing

Antiarrhythmic drugs may worsen ventricular arrhythmias in certain patients. This effect, termed proarrhythmia, aggravation or provocation of arrhythmia, can be investigated with either noninvasive or invasive techniques. Using electrophysiologic study, 160 patients with ventricular tachycardia or ventricular fibrillation were evaluated during treatment with 432 different antiarrhythmic regimens. Proarrhythmic responses were noted in 68 drug trials (16%), and at least 1 event was observed in 51 patients (32%). Nonsustained ventricular tachycardia was converted to sustained ventricular tachycardia in 17% of these studies. Hemodynamically stable ventricular tachycardia was converted to an arrhythmia that required cardioversion for termination in 5% of the studies. Ventricular tachyrhythmia was more easily induced in 12% of trials. These proarrhythmic responses were not related to changes in QRS duration, QT interval or JT interval measured at baseline or to changes produced by antiarrhythmic drugs.

Limitations of failure of procainamide during electrophysiologic testing to predict response to other medical therapy

To determine whether failure of procainamide to prevent initiation of ventricular tachyarrhythmias during electrophysiologic testing predicted failure of other antiarrhythmic regimens, 81 consecutive patients with coronary artery disease whose ventricular tachyarrhythmias remained inducible during procainamide administration were studied. Overall, 26 (12%) of 216 subsequent drug studies were successful and at least one effective drug regimen was identified in 22 (27%) of the 81 patients. Drug success was significantly related to the arrhythmia induced at baseline study; 7% of drug studies were successful in patients with sustained ventricular tachycardia, 24% in patients with ventricular fibrillation, and 29% in patients with nonsustained ventricular tachycardia. An effective drug regimen was found in 11 (19%) of 59 patients with sustained ventricular tachycardia, 4 (50%) of 8 patients with ventricular fibrillation and 7 (50%) of 14 patients with nonsustained ventricular tachycardia. In patients with sustained ventricular tachycardia, failure of procainamide to suppress the arrhythmia correlated with failure of other agents used singly but not in combination. This study supports the view that when procainamide fails to prevent initiation of the arrhythmia in patients with inducible sustained ventricular tachycardia it is unlikely that other individual standard agents will be effective. However, combination regimens may suppress the arrhythmia and should be evaluated. In patients with nonsustained ventricular tachycardia, all agents should be evaluated because failure to respond to procainamide does not predict subsequent responses to other agents either alone or in combination.

Report of the NASPE Mode Code Committee

The NASPE Mode Code Committee was formed in response to the growing need for efficient means of describing the function of increasingly complex single‐ and dual‐chamber cardiac pacemakers. After considering numeric, alphabetic, and pictorial codes, the Committee recommended the adoption of two codes: a generic code which is similar to the Revised ICHD Code and is suitable for conversational use, and a specific code, based on one developed by Brownlee and others, that permits more detailed specification of both antibradycardia and antitachycardia functions. The specific code described in this report was adopted by the NASPE Executive Advisory Committee as the NASPE Specific Code in March, 1983. The generic code was not adopted but is described herein for future reference in the light of experience to he gained in the use of the recently published Revised ICHD Code.

Utility of ambulatory electrocardiographic monitoring for predicting recurrence of sustained ventricular tachyarrhythmias in patients receiving amiodarone

The prognostic implications of changes in ventricular ectopic activity on serial 24 hour ambulatory electrocardiographic (Holter) recordings were prospectively evaluated in 107 patients with a history of sustained ventricular tachyarrhythmias treated with amiodarone for at least 30 days. Twenty-seven patients (25%) had insufficient ventricular ectopic activity (less than 10 ventricular premature complexes/h and no repetitive forms) on baseline Holter recordings for serial statistical analysis. In 53 (66%) of the remaining 80 patients, serial 24 hour Holter monitor recordings showed efficacy of treatment, defined as a 75% decrease in ventricular premature complexes, a 95% decrease in ventricular couplets and absence of ventricular tachycardia. During a mean follow-up period of 14.2 +/- 9.9 months, 34 (32%) of the 107 patients had recurrence of a sustained ventricular tachyarrhythmia. Holter recording correctly predicted nine recurrences and correctly identified 37 patients who did not experience a recurrence. Holter efficacy failed to predict recurrence of a sustained ventricular tachyarrhythmia in 16 patients, and 18 patients remained free of recurrence despite failure to achieve Holter efficacy. The positive predictive value of Holter monitoring efficacy was 33% and the negative predictive value was 70%; however, these differences were not statistically significant by chi-square analysis. Similar results were obtained using Holter recordings performed relatively early in therapy (6 weeks and 4 months). Of the 27 patients without significant ventricular ectopic activity on the baseline Holter recording, 9 had an arrhythmia recurrence despite continued infrequent ventricular premature complexes and no repetitive forms on subsequent recordings. The recurrence rate in this group (33%) was similar to the overall recurrence rate.(ABSTRACT TRUNCATED AT 250 WORDS)

Conversion from intravenous to oral mexiletine in the acute management of repetitive ventricular arrhythmia.

We evaluated the safety and efficacy of intravenous mexiletine and a method for converting from intravenous to oral mexiletine therapy. Fifteen patients with repetitive ventricular ectopy (13 had ventricular tachycardia) received intravenous mexiletine at a rate of 10 mg/min for 30 to 60 minutes. Ventricular ectopy was suppressed with minimal side effects in 10 of 15 subjects. Oral mexiletine was begun immediately after completion of the intravenous infusion at a dose of 10 mg/kg/24 hr in the 10 responders to intravenous therapy. In eight, the oral dose was effective in suppressing the arrhythmia, but it induced side effects in three of them. In one of these three, dose reduction resulted in adequate arrhythmia control with acceptable toxicity. In the two who did not respond to the original dose, a larger dose (15 mg/kg/24 hr) induced arrhythmia control with acceptable side effects in one subject. Thus rapid control of nonsustained repetitive ventricular arrhythmia can be achieved with intravenous mexiletine in about two thirds of patients, and conversion to oral therapy can often be achieved smoothly without significant arrhythmia recurrence.