Oral Sotalol Therapy Research Articles

Abstract 16208: Population Pharmacokinetics of Intravenously and Orally Administered Sotalol in Patients With Cardiac Arrhythmias

Introduction: Recently, an intravenous (IV) formulation of sotalol was approved to provide a loading dose before initiating oral sotalol therapy to reduce hospitalization days. However, the population pharmacokinetics (PK) of sotalol after administration of an IV loading dose regimen in patients with atrial fibrillation were not characterized. Understanding the PK of IV sotalol loading dose in patients with atrial fibrillation is required to ensure safety and optimal therapeutic outcomes. Hypothesis: The population PK model of IV and orally administered sotalol can be developed using data from two clinical PK studies with reasonable empirical Bayes estimates (EBEs) of PK parameters absorption rate constant (Ka), clearance (CL), and volume of distribution (Vd). Methods: The PK dataset of sotalol was from: 1) Relative bioavailability study with IV and oral sotalol PK data by sponsor AltaThera Inc., 2) Prospective Evaluation Analysis and Kinetics of IV Sotalol (PEAKS) registry study. Population PK was evaluated using NONMEM® 7.5, Perl-speaks-NONMEM (PsN®) version 5.3.0. Results: 545 sotalol concentrations in 25 patients were analyzed. A one-compartment model with a first-order elimination rate best described the data (Figure 1). The data correlated QTc interval levels within the observed sotalol concentration range (1.2 to 1900 ng/mL) were below 500 ms. In the final model, the EBE’s of sotalol PK parameters were, Ka - 1.44 hr -1 , CL 0.46 - L/h/kg, and the Vd -5.6 L/kg. Further PK/PD studies are needed to establish the correlation between sotalol PK and safety in this population. Conclusions: The PK of sotalol after IV and oral doses were adequately described using a population PK modeling approach. The QTc levels correlated to the plasma concentrations in this study were within the safety limit of 500 ms. This population PK model could be used to correlate the PK with safety (QTc interval prolongation) further to optimize the sotalol IV and oral dosing regimen.

Feasibility and Safety of Intravenous Sotalol Loading in Adult Patients With Atrial Fibrillation (DASH-AF)

BackgroundInpatient initiation of sotalol is recommended owing to its proarrhythmic effects. ObjectivesThe DASH-AF (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation) trial evaluates the safety and feasibility of intravenous (IV) sotalol, achieving a steady state with maximum QTc prolongation within 6 hours instead of the traditional 5-dose inpatient oral (PO) titration. MethodsDASH-AF is a prospective, nonrandomized, multicenter, open-label trial consisting of patients who underwent IV sotalol loading dose to initiate rapid oral therapy for atrial arrhythmias. IV dose was calculated based on the target oral dose as indicated by baseline QTc and renal function. Patients’ QTc (in sinus) was measured via electrocardiography at 15-minute intervals and after IV loading completion. Patients were discharged 4 hours after first oral dose. All patients were monitored via mobile cardiac outpatient telemetry for 72 hours. The control group was composed of patients admitted for the traditional 5 PO doses. Safety outcomes were assessed in both groups. ResultsA total of 120 patients from 3 centers were enrolled from 2021 to 2022 in the IV loading group (compared with type of AF– and renal function–matched patients in the conventional PO loading cohort). This study demonstrated no significant change in ΔQTc in both groups, with a significantly lower number of patients requiring dose adjustment in the IV arm compared with the PO arm (4.1% vs 16.6%; P = 0.003). This led to potential cost savings of up to $3,500.68 per admission. ConclusionsThe DASH-AF trial shows that rapid IV sotalol loading in atrial fibrillation/flutter patients for rhythm control is feasible and safe compared with conventional oral loading with significant cost reduction. (Feasibility and Safety of Intravenous Sotalol Administered as a Loading Dose to Initiate Oral Sotalol Therapy in Adult Patients With Atrial Fibrillation [DASH-AF]; NCT04473807)

Abstract 14826: Single Day Intravenous Sotalol as a Loading Dose to Initiate Oral Sotalol Therapy: Is it Safe and Efficacious?

Introduction: Due to pro-arrhythmic effects associated with Sotalol, inpatient initiation with QTc monitoring for five doses is recommended. An IV loading dose followed by two oral doses has been shown to achieve steady-state concentrations. Hypothesis: To evaluate the safety of single day loading of IV sotalol in patients with atrial fibrillation and atrial flutter (AF/AFL). Methods: We prospectively evaluated 40 patients at our institution who received IV sotalol as single day loading dose for initiation of oral sotalol therapy for AF/AFL. IV sotalol dose was calculated based on target oral dose as indicated by baseline QTc interval and renal function. Patients' QTc (in sinus) was measured via ECG on 15 minutes intervals and after IV loading completion. Loading was considered complete after second oral dose. All patients were monitored via a mobile cardiac outpatient monitor for 3 days followed by a final 12 ECG. Results: A total of 40 patients were included in the study. The mean age was 69 + 8.2 years, 78.9% of patients were men. QTc significantly increased from 435.9 + 26.4 to 462.9 + 31.6 with following IV loading (p<0.001), that stabilized following oral loading completion (450.63 + 44.4; p=0.12). There were no cases of severe bradycardia, sinus node dysfunction, ventricular arrhythmias. reported. Conclusions: Our study sheds evidence that rapid IV sotalol loading in AF/AFL is safe and efficacious. This will not only provide patient convenience but will lead to reduced economic burden on patients and health care systems.

Abstract 14804: Are Mobile Cardiac Outpatient Monitors Reliable to Monitor Qtc in Comparison to 12 Lead ECG

Introduction: Use of mobile cardiac outpatient monitor (MCOT) increased during the COVID-19 pandemic as a substitute for telemetry and monitoring of arrythmias during loading of antiarrhythmic drugs (AAD). However, data comparing difference of QTc interval between a MCOT, and 12 lead ECG is scare. Hypothesis: To assess the accuracy of mobile cardiac outpatient monitor in comparison to 12 lead ECG for QTc monitoring Methods: We prospectively evaluated 24 patients at our institution who received IV sotalol as single day loading dose for initiation of oral sotalol therapy for atrial fibrillation/atrial flutter (AF/AFL). All patients were discharged 6 hours after the IV loading dose with a MCOT for 3 days. All patients had a 12 lead ECG within 12-18 hours of the baseline line MCOT transmission. Variation in heart rate and QTc was assessed. Results: A total of 24 patients were included in the study. The mean age was 65 + 7.3 years, 80% of patients were men. The mean difference between the QTc interval measured on 12 lead ECG and MCOT was 5.1 + 6 milliseconds [450 + 33 (EKG) - 445 + 39 (MCOT)], p=0.92. The mean heart rate difference between the two modalities was also not significant, p=0.726 [ 70.4 + 19 (EKG) -72 + 11.8 (MCOT), ΔHR=1.6 + 7.2 beats per minute]. Conclusions: MCOT can be considered as a reliable alternate to 12 lead ECG for monitoring of QTc in patients receiving AAD.

Abstract 12650: A Faster and Safe Way for Dose Escalation of Sotalol Therapy in Patients With Atrial Fibrillation or Flutter

Sotalol is frequently employed to prevent the recurrence of highly symptomatic atrial fibrillation or flutter, but recurrence is not unusual and may require dose escalation. Sotalol can cause QTc prolongation proportional to blood concentration and at times may cause Torsade de Pointes ventricular tachycardia (TdP). Because the risk of TdP, dose escalation of oral sotalol therapy is mandated by FDA to be in-hospital for a minimum of 3 days under ECG monitoring with facilities and personnel able to provide cardiac resuscitation. With oral administration (bid), 3 days are needed to reach the new maximal steady-state blood concentrations (Cmax ss) and thus maximal QTc . Three hospital days in a telemetry bed is costly of time and resources. IV sotalol makes it possible to reduce the escalation time from 3 days to 1 day. The IV to oral dose escalation has been developed by model informed drug development. Serum sotalol concentrations and corresponding QTc were obtained from a bioequivalence study in healthy volunteers who received a single dose of oral and IV sotalol. NONMEM software package was used for population pharmacokinetic modeling and simulation. First Order Conditional Estimation method with Interaction (FOCE-INTER) was used for computation. We chose to administer IV sotalol over 1 hour to obtain the new Cmax ss target in a timeframe convenient for medical staff to supervise. Simulation for dose escalation from 80 to 120 mg bid is shown in the Figure; 75 mg IV sotalol is administered over 1 hour followed by 120 mg oral sotalol at 5 hours from start of infusion, then a second oral dose of 120 mg at 12 hours. One can target escalation from 120 to 160 mg by loading 90 mg IV over 1 hr followed by 160 mg oral dosing. Sotalol concentration will peak in 2-4 hours following each oral administration, thus in 21 hour there will be 3 sotalol peak concentrations. This permits evaluation of QTc response and risk of TdP all within a 1 day admission.

Abstract 12649: A Faster and Safe Way to Initiate Sotalol Therapy for Patients With Atrial Fibrillation or Flutter

Sotalol drug therapy is frequently employed to prevent the recurrence of highly symptomatic atrial fibrillation or flutter (AF, AFb). Sotalol can cause QTc prolongation that is proportional to blood concentration. Excessive concentration can cause Torsade de Pointes ventricular tachycardia (TdP). Because the risk of TdP, initiation of oral sotalol therapy is mandated by FDA to be in-hospital for a minimum of three days under ECG monitoring with facilities and personnel able to provide cardiac resuscitation. With oral administration (bid), 3 days are needed to reach maximal steady-state blood concentrations (Cmax ss) and thus maximal QTc prolongation. Three hospital days in a telemetry bed is costly and considerable expenditure of time and resources. Availability of IV sotalol makes it possible to reduce the loading time from 3 days to 1 day. The IV to oral loading regimen has been developed by model informed drug development. Serum sotalol concentrations and corresponding QTc were obtained from a previously performed bioequivalence study in healthy volunteers who received a single dose of oral and IV sotalol. NONMEM software package was used for population pharmacokinetic modeling and simulation. First Order Conditional Estimation method with Interaction (FOCE-INTER) was used for computation. We chose to administer IV sotalol over 1 hour to obtain Cmax ss target in a timeframe convenient for medical staff to supervise. The simulation for loading to the Cmax target produced by 80 mg PO bid is shown in the Figure; 60 mg IV sotalol is administered over 1 hour followed by 80 mg oral sotalol at 5 hours from start of infusion end then a second oral dose of 80 mg at 12 hours. One can target 120 mg maintenance dose by loading 90 mg IV over 1 hr followed by 120 mg oral dosing. Sotalol concentration will peak in 2-4 hours following each oral administration, thus in 21 hour there will be 3 sotalol peak concentrations. This permits evaluation of QTc response and risk of TdP all within a 1 day admission.

Sotalol: A rescue drug in the face of life-threatening refractory ventricular tachycardia

We describe postoperative refractory ventricular tachycardia (VT) in a patient following aortic and mitral valve replacement. Following an uneventful separation from cardiopulmonary bypass with dobutamine, the patient developed recurrent VT, 4 hours into the postoperative period. The VT did not respond to standard doses of xylocard, magnesium and amiodarone. Electrolyte and acid base parameters were normal. Multiple cardioversions failed to revert back to a stable rhythm. Intra-aortic balloon pumping was instituted and overdrive right ventricular pacing was unsuccessful. Following intravenous sotalol 80 mg, the VT came under control and reverted to a nodal rhythm, which required atrial pacing for the next 8 hours. Oral sotalol therapy was continued at 40 mg daily. The VT did not recur.

EFFICACY OF DUAL STRATEGY OF SOTALOL AND ELECTRICAL CARDIOVERSION WITH BALLOON MITRAL VALVOTOMY IN PERSISTENT RHEUMATIC ATRIAL FIBRILLATION WITH MITRAL STENOSIS

ObjectivesA few studies has shown that achievement of normal sinus rhythm (NSR) with amiodarone alone or in combination with direct current (DC) cardioversion is effective and superior to ventricular rate...

Sustained torsade de pointes occurring early during oral sotalol therapy for atrial fibrillation recurrence prophylaxis in a patient without heart disease

This report describes a 64 year-old female patient admitted to our department for recurrent and symptomatic episodes of atrial fibrillation. Antiarrhythmic therapy with sotalol at 240 mg/day was started, and after 48 h the patient experienced several episodes of sustained torsade de pointes, dramatic marked QT interval prolongation and negative T wave, in absence of overt cardiac disease, renal failure, electrolyte abnormalities or baseline QT interval prolongation. This case emphasizes the importance of hospitalization at the starting of sotalol therapy, especially in female patients, even in absence of predisposing factors for drug-induced tachyarrhythmias.

Meta-analysis of the Risk of Torsades de Pointes in patients treated with intravenous racemic sotalol.

Intravenous (IV) racemic sotalol is useful for the treatment of multiple tachydysrhythmias. The authors hypothesized that the risk of torsades de pointes (TdP) in patients treated with a single IV infusion of sotalol is lower than the 2-4% risk associated with chronic oral sotalol therapy. A MEDLINE search under the subject heading "sotalol" was made of all publications involving humans written in English or German from 1966 to October 1, 2000. A meta-analysis of all original reports including patients who were given a single infusion of at least 1.5 mg/kg or 100 mg of IV sotalol over 30 minutes or less was performed. Potential variables predictive of TdP were assessed. The primary outcome was the observation of TdP associated with IV sotalol infusion. Secondary measurements included hypotension, bradycardia, and worsening of congestive heart failure. All excluded studies and case reports were also examined for evidence of TdP associated with IV sotalol treatment. The search included 1,005 publications. There were 37 reports in which 962 patients received IV sotalol and met the inclusion criteria. There was one report of self-terminating TdP lasting 10 seconds among the 962 patients included in the study. There was no report of TdP associated with only IV racemic sotalol administration in any of the excluded studies. If it is assumed that the risk of TdP is homogeneous in the population of patients treated with IV sotalol, then based on the 962 included patients, the rate of TdP is 0.1% (95% CI = 0.003% to 0.6%). The overall risk of TdP in patients treated with a single infusion of IV sotalol is low compared with that in patients given chronic oral sotalol therapy.

Long-term results of electrophysiologically guided sotalol therapy for life-threatening ventricular arrhythmias

The efficacy and safety of sotalol therapy for ventricular arrhythmias was evaluated in 133 patients with drug-refractory ventricular arrhythmias. All patients had baseline electrophysiologic studies before and after oral sotalol therapy. Sixty-six patients were discharged home, treated with sotalol (52 patients without inducible ventricular tachycardia or fibrillation and 14 patients with hemodynamically stable inducible ventricular tachycardia). The mean follow-up period was 41 ± 27 months for the 14 patients with hemodynamically stable ventricular tachycardia. Sotalol was effective in 8 of these 14 patients. Recurrent nonlethal ventricular tachycardia occurred in 3 patients; 2 patients had sudden death; and 1 patient had adverse side effects. The 52 patients without inducible ventricular tachycardia were followed up for a mean period of 36 ± 30 months. Thirty-five of 52 patients were successfully treated. Two patients had recurrent ventricular tachycardia; both of these episodes of ventricular tachycardia occurred within the first year. Four patients had sudden cardiac death; three of these deaths occured within the first month, and the last episode of sudden death occurred after 8 years of sotalol therapy. The actuarial incidence of sotalol efficacy was 76% at 1 year, 72% at 2 years, 64% at 4 years, and 52% at 5 years. Approximately 46% of patients receiving long-term sotalol treatment reported side effects. Side effects severe enough to warrant withdrawal of sotalol occurred in 7 (11%) patients. The results of our study suggests that sotalol is effective for selected patients with drug refractory ventricular arrhythmias. Although the incidence of side effects are high, patients appear to tolerate long-term sotalol therapy well.

911-36 Safety and Efficacy of Sotalol in Drug Refractory Atrial Fibrillation/Flutter

The clinical efficacy and safety of oral Sotalol in patients (pts) with refractory atrial fibrillation/flutter (AF) has not been widely examined. We evaluated 31 pts with chronic (8 pts) or paroxysmal (23 pts) AF, 20 males, mean age 61 ± 8 yrs, LV ejection fraction was < 40 in 11 pts, coronary artery disease in 11 pts, cardiomyopathy in 5 pts, valvular heart disease in 3 pts, no structural heart disease in 12 pts. All pts had failed multiple 2.7 (range 1 – 4) antiarrhythmic drug trials. Oral Sotalol therapy was commenced during AF in 15 pts and in sinus rhythm in 16 pts and was titrated to maximally tolerated or effective levels. All pts underwent 24 hr Holter monitor prior to discharge. Sotalol resulted in conversion to sinus rhythm in 12 of 15 (80%) pts. 2 pts had recurrent AF. and 1 pt developed side effects while in the hospital. 28 pts were discharged on a mean dose of 220 mg daily (range 80 – 320). During followup of 8.2 mas (range 2 – 20) there were no sudden or cardiac deaths. None of the pts demonstrated proarrhythmia on Holter monitor. 4 pts (12%) had recurrence of AF. Sotalol was discontinued in 3 pts (S%) due to side effects. 22 of 31 pts (71%1 were free of recurrent AF and side effects during followup. (1) Sotalol is effective, safe and well tolerated for acute conversion of AF to sinus rhythm as well as maintenance of sinus rhythm. (2) Incidence of adverse effects including proarrhythmia is low in this pt population. (3) Effective dose of Sotalol for control of AF seems to be lower than for ventricular tachycardia.

Multicenter trial of sotalol compared with procainamide in the suppression of inducible ventricular tachycardia: A double-blind, randomized parallel evaluation

Sotalol is the prototype class III agent that combines β-blocking properties with the propensity to prolong the effective refractory period by lengthening the action potential duration. Its precise effect on the prevention of ventricular tachycardia-ventricular fibrillation (VTVF) compared to class I agents has not been evaluated in a blinded study. In a double-blind parallel-design multicenter study, the electrophysiologic and antiarrhythmic effects of intravenous and oral sotalol (n = 55) and procainamide ( n = 55) were therefore compared in patients with VTVF inducible by programmed electric stimulation. Sotalol produced a greater effect on lengthening the ventricular effective refractory period (VERP). It prevented the inducibility of VTVF in 30% versus 20% for procainamide, but this was not significantly different. In an alternate therapy group ( n = 41) of similar patients previously refractory to or intolerant of procainamide, intravenous sotalol prevented inducibility in 32%. The pooled overall sotalol efficacy rate was 31%. There was a significant relation between the increase in the VERP and the prevention of inducibility of VTVF ( n = 56; p < 0.02). VERP of ≥300 msec was critical for the prevention of VTVF inducibility. Thirteen sotalol and 6 procainamide responders from the randomized group and 30 from the nonrandomized groups completed 1 year of oral sotalol therapy follow-up. Life-table analysis of these patient in each group showed a trend in favor of sotalol; however, statistical analysis was not possible because of the small numbers of patients. Both sotalol and procainamide were well tolerated. In the randomized group there was one case of sudden death during treatment with sotalol and two cases of nonfatal torsades de pointes in the procainamide group and two in the sotalol group; in the nonrandomized alternate therapy group, there were 6 cases of nonfatal torsades de pointes. The data support the emerging role of sotalol in the control of symptomatic ventricular tachycardia and fibrillation.

Efficacy of intravenous sotalol for suppressing inducibility of supraventricular tachycardias at rest and during isometric exercise

The efficacy of intravenous sotalol (1 mg/kg) for suppressing inducibility of supraventricular tachycardias (SVT) with different electrophysiologic mechanisms was studied in 30 consecutive patients referred for an electrophysiologic study because of paroxysmal SVT. Orthodromic SVT using accessory atrioventricular (AV) connection was inducible in 14 patients, AV nodal reentrant SVT in 8, and intraatrial SVT in 8 before administration of sotalol. Isometric handgrip exercise facilitated the inducibility of SVT in 8 patients who were noninducible at rest. After intravenous sotalol, 7 of 14 patients (50%) with orthodromic SVT, 8 of 8 (100%) with AV nodal reentrant SVT, and 8 of 8 (100%) with intraatrial reentrant SVT became noninducible into sustained SVT. Isometric exercise facilitated the inducibility of only 3 nonsustained SVT runs after sotalol infusion, and exercise did not reverse the prolongation of refractory periods of the atrium, AV node, accessory pathway and ventricle caused by sotalol. During a mean follow-up period of 18 ± 7 months, none of the 14 patients who remained noninducible into sustained SVT during the stress test after intravenous sotalol and tolerated long-term oral sotalol therapy had recurrence of symptomatic SVT. Thus, sotalol is efficacious for suppressing SVT with AV nodal or intraatrial reentrant mechanism, but less efficacious in patients with accessory AV pathway. The β-blocking and cellular antiarrhythmic effects of sotalol are not significantly reversed by exercise.

Concentration dependence of class III and beta-adrenergic blocking effects of sotalol in anesthetized dogs

Sotalol is unique among beta-adrenergic blocking drugs in possessing significant class III antiarrhythmic actions. The present study was designed to assess the relative concentration dependence of beta-blocking and class III actions of sotalol and to relate the findings to concentrations achieved during oral sotalol therapy in humans. Measurements were made in anesthetized dogs under control conditions, and then in the presence of a series of stable sotalol plasma concentrations produced by sequential loading and maintenance infusions.Beta-blocking effects of sotalol, determined by attenuation of the chronotropic actions of isoproterenol, were seen at the lowest dose used. Increases in atrial and ventricular refractory periods (observed in dogs with autonomic blockade to exclude beta-receptor-mediated or reflex autonomic effects) required much larger doses of sotalol. Half-maximal beta-blocking effects occurred at an average sotalol concentration of 0.8 ± 0.3 mg/liter, an order of magnitude lower than the concentrations required for half-maximal effects on atrial (6.9 ± 1.2 mg/liter, p < 0.01) and ventricular (6.8 ± 2.8 mg/liter, p < 0.05) refractoriness.These results show that substantially higher concentrations are needed for the class III effects of sotalol than for its beta-blocking action. These pharmacodynamic differences need to be considered in evaluating the antiarrhythmic efficacy and mechanisms of this unusual drug.

Comparison of the effects of chronic oral therapy with atenolol and sotalol on ventricular monophasic action potential duration and effective refractory period

The effects of 4 weeks' therapy with atenolol, 50 mg twice daily, and sotalol, 160 mg twice daily, on ventricular monophasic action potential duration (MAPD 90) and effective refractory period (VERP) are compared in a randomized cross-over study in 10 patients with stable angina pectoris undergoing elective cardiac catheterization. At matched ventricular pacing cycle lengths (range 500 to 1000 msec), MAPD 90 was 29 to 42 msec (11.5% to 13.4%) longer and VERP was 21 to 32 msec (8.9% to 11.4%) longer on oral sotalol than on oral atenolol. Intravenous sotalol (100 mg) caused a significant lengthening of MAPD 90 and VERP during oral atenolol therapy, while intravenous atenolol (10 mg) had no additional effect during oral sotalol therapy. The effects of sotalol on ventricular repolarization and refractory period persist over and above any adaptational response to beta-receptor blockade that may occur during chronic therapy.

Electrophysiologic and antiarrhythmic efficacy of oral sotalol for sustained ventricular tachyarrhythmias: Evaluation by programmed stimulation and ambulatory electrocardiogram

Programmed ventricular stimulation and ambulatory electrocardiography were performed both before and during oral sotalol therapy in 39 patients with ventricular tachyarrhythmia inducible by programmed stimulation (sustained ventricular tachycardia [n = 31], ventricular fibrillation [n = 3], nonsustained ventricular tachycardia [n = 5]). Oral sotalol was started at 80 mg twice daily and the dose thereafter was then gradually increased until a mean daily dose of 300 mg (range 160-480) was reached. In 12 of 34 patients with inducible sustained ventricular tachycardia or fibrillation the arrhythmia was suppressed; in 19 patients it was not and in 3 the spontaneous arrhythmia recurred. Reproducibly inducible nonsustained ventricular tachycardia was suppressed by sotalol in all five patients with this arrhythmia. Thus, a favorable electrophysiologic response was obtained in 17 (44%) of 39 patients. Arrhythmia suppression correlated with the type of arrhythmia (unsustained or sustained) induced during the control period (p less than 0.05), and nonresponders had a higher incidence of previously ineffective drug trials (p less than 0.05). In 22 patients treated long term with sotalol suppression of arrhythmia inducibility on programmed stimulation predicted freedom from recurrences (16 of 17), whereas continued inducibility indicated drug failure (5 of 5) (p less than 0.005). Serial ambulatory electrocardiograms performed in 37 of the 39 patients did not correlate with the results of electrophysiologic testing. For the patients on long-term treatment, invasive testing was superior to electrocardiographic monitoring in predicting outcome. These data indicate that in daily doses of 160 to 480 mg oral sotalol is a very useful agent in patients presenting with sustained ventricular tachycardia or fibrillation, and its efficacy is fairly well predicted by programmed stimulation.