Calcium channel antagonism reduces exercise-induced ventricular arrhythmias in catecholaminergic polymorphic ventricular tachycardia patients with RyR2 mutations

Calcium channel antagonism in RyR2 defects. INTRODUCTION: Recently, gain-of-function mutations of cardiac ryanodine receptor RyR2 gene have been identified as a cause of familial or catecholaminergic polymorphic ventricular tachycardia. We examined the influence of the calcium channel blockers, verapamil and magnesium, on exercise-induced ventricular arrhythmias in patients with RyR2 mutations. METHODS AND RESULTS: Six molecularly defined catecholaminergic polymorphic ventricular tachycardia patients, all carrying a RyR2 mutation and on beta-adrenergic blocker therapy, underwent exercise stress test four times: at baseline, after verapamil and magnesium sulphate infusions, and finally, without interventions. The number of isolated and successive premature ventricular complexes during exercise ranged from 40 to 374 beats (mean 165 beats) at baseline, and was reduced during verapamil by 76+/-17% (P<0.05). Premature ventricular complexes appeared later and at higher heart rate during verapamil than at baseline (119+/-21 vs. 127+/-27 min-1, P<0.05). Magnesium did not inhibit the arrhythmias. Results in the fourth exercise stress test without interventions were similar to those in the first baseline study. CONCLUSIONS: This study provides the first in vivo demonstration that a calcium channel antagonist, verapamil, can suppress premature ventricular complexes and nonsustained ventricular salvoes in catecholaminergic polymorphic ventricular tachycardia caused by RyR2 mutations. Modifying the abnormal calcium handling by calcium antagonists might have therapeutic value.     

Ten-Year Follow-Up of Cardiac Sympathectomy in a Young Woman with Catecholaminergic Polymorphic Ventricular Tachycardia and an Implantable Cardioverter Defibrillator

Current recommendations for therapy of catecholaminergic ventricular tachycardia (CPVT) include beta blockade and implantable cardioverter defibrillators (ICDs). Patients may experience recurrent arrhythmias, ICD shocks and, rarely, sudden death despite optimal medical therapy. We report a young woman with CPVT who received frequent ICD shocks despite beta blockade, who subsequently underwent cardiac sympathectomy with a dramatic reduction in shocks over 10 years of follow-up.     

Sudden death in a young man with catecholaminergic polymorphic ventricular tachycardia and paroxysmal atrial fibrillation

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a familial condition that presents with exercise-induced syncope or sudden death in children or young adults. In most cases the disease is caused by a mutation in the cardiac ryanodine receptor (RyR2) gene. Current evidence suggests that primary therapy for CPVT is beta blockade and implantable cardioverter defibrillator (ICD) placement. There is a recent report of a patient with CPVT who died despite appropriate ICD therapies, and we report a similar case. Our patient died after probably initially receiving inappropriate ICD shocks for atrial fibrillation. We recommend that utmost efforts should be made to prevent shocks including repeated exercise testing to confirm suppression of PVT.     

Catecholaminergic polymorphic ventricular tachycardia

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a highly malignant form of arrhythmogenic disorder characterized by exercise- or emotional-induced polymorphic ventricular tachycardia in the absence of detectable structural heart disease. Because of the typical pattern of arrhythmias (bidirectional ventricular tachycardia and the occurrence and severity of arrhythmia correlated well with exercise workload) during exercise stress test, CPVT can be identified promptly. Molecular genetic screening of the genes encoding the cardiac ryanodine receptor and calsequestrin is critical to confirm uncertain diagnosis of CPVT. With the exception of beta-blockers, no pharmacologic therapy of proven effectiveness is available: although beta-blockers reduce the occurrence of ventricular tachycardia, 30% of patients treated with beta-blockers still experience cardiac arrhythmias and eventually require implantable cardioverter defibrillator implantation to prevent cardiac arrest.     

La flecainida reduce las arritmias ventriculares en pacientes con taquicardia ventricular polimórfica catecolaminérgica genotipo RyR2 positivo

Introduction and objectives

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by polymorphic or bidirectional ventricular arrhythmias (VA) triggered by physical or emotional stress in young people with a structurally normal heart. Beta-blockers are the cornerstone of treatment, while flecainide has recently been incorporated into the therapeutic arsenal. The aim of this study was to report our experience with this drug.

Mechanism underlying catecholaminergic polymorphic ventricular tachycardia and approaches to therapy

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmia syndrome characterized by VT induced by adrenergic stress in the absence of structural heart disease and high incidence of sudden cardiac death. The diagnosis is made based on reproducible ventricular tachyarrhythmias including bidirectional VT and polymorphic VT during exercise testings. Two causative genes of CPVT have been identified: RYR2, encoding the cardiac ryanodine receptor (RyR2) Ca²⁺ release channel, and CASQ2, encoding cardiac calsequestrin. A mutation in RYR2 or CASQ2 is identified in approximately 60% of patients with CPVT. Mutations in these two genes destabilize the RyR2 Ca²⁺ release channel complex in sarcoplasmic reticulum and result in spontaneous Ca²⁺ release through RyR2 channels leading to delayed after depolarization, triggered activity, and bidirectional/polymorphic VT. Implantable cardioverter defibrillators (ICDs) are recommended for prevention of sudden death in patients with CPVT.1. A.E. Epstein, J.P. DiMarco, K.A. Ellenbogen, et al., ACC/AHA/HRS 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the ACC/AHA/NASPE 2002 Guideline Update for Implantation of Cardiac Pacemakers and Antiarrhythmia Devices): developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. Circulation. 2008;117:e350 However, painful shocks can trigger further adrenergic stress and arrhythmias, and deaths have occurred despite appropriate ICD shocks. Treatment with β-adrenergic blockers reduces arrhythmia burden and mortality, but is not completely effective. The beneficial effects of Ca²⁺ channel blocker verapamil in combination with β-blocker have been reported, but the role of verapamil has not been well assessed. Because Ca²⁺ leakage through ryanodine channel is a common mechanism of CPVT, ryanodine channel block may have a therapeutic effect. We discovered that flecainide directly inhibits RyR2 channels and prevent CPVT. Left cardiac sympathetic denervation may be an effective alternative treatment in combination with ICD, especially for patients whose arrhythmias are not controlled by drug therapies.     

Benefit of Pacing and Beta-Blockers in Idiopathic Repetitive Polymorphic Ventricular Tachycardia

An 18-year-old woman presented with recurrent exercise-induced syncopal episodes and severe systolic dysfunction. ECG monitoring disclosed repetitive polymorphic ventricular complexes, paroxysms of bidirectional ventricular tachycardia, and nonsustained bursts of slow polymorphic ventricular tachycardia that increased in length and rate during exercise. Ventricular arrhythmias were refractory to medical treatment, which included verapamil and beta-blockers. Addition of permanent atrial pacing to beta-blocker therapy suppressed the arrhythmias and reversed systolic impairment in the following months.     

Appropriate ICD therapy in patients with idiopathic dilated cardiomyopathy: long term follow-up

The implantable cardioverter defibrillator (ICD) has proved effective in preventing sudden death and decreasing mortality in randomised secondary prevention trials. Some nonrandomized studies have reported different incidences and predictors of appropriate ICD therapy in patients with idiopathic dilated cardiomyopathy (DCM). The antiarrhythmic and other medical therapies were different between the published studies and it was reported that not using beta-blockers was a predictor of appropriate ICD therapy. In the present study, we report on our long-term experience with ICD therapy in patients with DCM, the majority of whom were treated with beta-blockers and amiodarone. The study population consisted of 25 patients with DCM who underwent initial transvenous ICD implantation between December 1995 and May 2005. Indications for ICD implantation were monomorphic sustained ventricular tachycardia (VT) in 16 patients (64%), cardiac arrest in 8 patients (32%), and syncope plus inducible VT in one patient. Twenty-four patients underwent an electrophysiologic study (EPS). In 18 patients, the ICDs were programmed to only shocks and in 7 patients an additional antitachycardia pacing program was performed. One patient was lost to follow-up and 24 patients were followed-up primarily in our ICD pacemaker outpatient clinic. Appropriate ICD therapy was defined as antitachycardia pacing therapy or shock for tachyarrhythmia determined by evaluation of the clinical information and by device diagnostics to be either ventricular fibrillation or ventricular tachycardia. The mean follow-up was 39.29 +/- 30.59 months after ICD implantation. At follow-up, 17 patients were using a beta-blocker and 16 patients amiodarone. Appropriate ICD therapy was observed in 14 patients (58%). The detected arrhythmias were VT in 12 patients, ventricular fibrillation (VF) in one, and VT and VF in one patient. The time to first ICD therapy was 15.93 +/- 18.45 (range, 1-74) months. Using the Kaplan-Meier method, the percent survival free of appropriate ICD therapy was 82%, 72%, 66%, and 55% at 1, 2, 3, and 4 years follow-up, respectively. The clinical, echocardiographic, and electrophysiologic characteristics did not differ between those who did and did not receive appropriate ICD therapy. However, the mean QRS duration was significantly longer in patients who received appropriate ICD therapies. Cox regression analysis did not reveal any factors that predicted appropriate ICD therapy. Five patients (21%) died during follow-up. Four deaths were classified as cardiac and one as noncardiac. The cumulative survival from total death was 94%, 82%, 82%, and 69%, and the cumulative survival from cardiac death was 94%, 82%, 82%, and 76% during 1, 2, 3, and 4 years of follow-up, respectively. In summary, in this selected patient population with DCM, the majority of patients were unresponsive to beta-blocker and antiarrhythmic therapy. Most of these patients received appropriate ICD therapy during follow-up. Cox regression analysis did not identify any factors that predicted appropriate ICD therapy. Additional trials with larger patient populations are needed to detect the predictors of appropriate ICD therapy in patients with DCM.     

Bidirectional ventricular tachycardia and fibrillation elicited in a knock-in mouse model carrier of a mutation in the cardiac ryanodine receptor

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited disease characterized by adrenergically mediated polymorphic ventricular tachycardia leading to syncope and sudden cardiac death. The autosomal dominant form of CPVT is caused by mutations in the RyR2 gene encoding the cardiac isoform of the ryanodine receptor. In vitro functional characterization of mutant RyR2 channels showed altered behavior on adrenergic stimulation and caffeine administration with enhanced calcium release from the sarcoplasmic reticulum. As of today no experimental evidence is available to demonstrate that RyR2 mutations can reproduce the arrhythmias observed in CPVT patients. We developed a conditional knock-in mouse model carrier of the R4496C mutation, the mouse equivalent to the R4497C mutations identified in CPVT families, to evaluate if the animals would develop a CPVT phenotype and if beta blockers would prevent arrhythmias. Twenty-six mice (12 wild-type (WT) and 14RyR(R4496C)) underwent exercise stress testing followed by epinephrine administration: none of the WT developed ventricular tachycardia (VT) versus 5/14 RyR(R4496C) mice (P=0.02). Twenty-one mice (8 WT, 8 RyR(R4496C), and 5 RyR(R4496C) pretreated with beta-blockers) received epinephrine and caffeine: 4/8 (50%) RyR(R4496C) mice but none of the WT developed VT (P=0.02); 4/5 RyR(R4496C) mice pretreated with propranolol developed VT (P=0.56 nonsignificant versus RyR(R4496C) mice). These data provide the first experimental demonstration that the R4496C RyR2 mutation predisposes the murine heart to VT and VF in response caffeine and/or adrenergic stimulation. Furthermore, the results show that analogous to what is observed in patients, beta adrenergic stimulation seems ineffective in preventing life-threatening arrhythmias.     

Concomitant beta-blocker therapy is associated with a lower occurrence of ventricular arrhythmias in patients with decompensated heart failure

BACKGROUND: Ventricular arrhythmias are nearly universally present in patients with advanced congestive heart failure (CHF) and represent an important cause of mortality in these patients. One of the putative mechanisms for the salutary effects of beta-blockers on sudden death mortality in heart failure is their ability to suppress ventricular arrhythmias. However, supporting data in patients with CHF are sparse, especially in the setting of excessive neurohumoral activation associated with symptomatic decompensated heart failure. METHODS AND RESULTS: We studied 236 patients (159 men; mean age, 61 +/- 14 years) admitted for decompensated CHF. Fifty patients were receiving beta-blockers at the time of the study. The severity of ventricular arrhythmia was assessed by 24-hour Holter recordings by using several prospectively defined measures of ventricular ectopy. All measures of ventricular ectopy were lower in patients receiving beta-blockers. The average hourly total premature ventricular beats (PVCs), hourly ventricular couplets, repetitive PVCs, and frequency of ventricular tachycardia episodes were 15% (P =.02), 75% (P <.05), 72% (P <.05), and 87% (P =.01) lower in patient receiving beta-blockers, respectively. In a multivariate regression analysis, the negative relationship between beta-blockers and the average hourly PVCs (P =.03), the frequency of ventricular pairs (P =.03), repetitive PVCs (P <.05), and ventricular tachycardia episodes (P =.01) remained significant and independent. CONCLUSIONS: Concomitant beta-blocker therapy during heart failure decompensation is associated with a marked reduction in complex ventricular ectopy and episodes of ventricular tachycardia. This effect of beta-blockers may play an important protective role by preventing serious ventricular arrhythmias during transient increases in sympathetic activity.     

Efficacy of verapamil in exercise-induced ventricular tachycardia

The antiarrhythmic efficacy of verapamil was determined by serial treadmill testing in 16 patients with reproducible exercise-induced ventricular tachycardia (VT). Twelve of the 16 patients responded to verapamil, 0.2 mg/kg intravenously; in 8 of these 12 responders, an oral verapamil regimen of 160 to 320 mg given every 8 hours also prevented exercise-induced VT. Plasma verapamil concentration was significantly higher in the responders than in the nonresponders to intravenous verapamil, but levels were similar in responders and nonresponders to oral therapy. The 8 responders to the oral drug were followed up while receiving verapamil therapy for 6 to 22 months (mean 15), and exercise-induced VT did not recur in any patient. Five of the 8 responders also had concomitant spontaneous VT unrelated to exercise which verapamil suppressed initially as well: 4 remained free of spontaneous VT, while 1 patient had recurrence of spontaneous VT. Thus, in patients with exercise-induced VT, verapamil is a promising alternative therapy to beta-adrenergic blocking agents. The effectiveness of verapamil is consistent with a mechanism of arrhythmogenesis involving calcium channels.     

Clinical outcome of acute myocardial infarction in patients on treatment with beta-blockers or calcium antagonists. A study of 7,922 hospitalized first myocardial infarctions.

To assess the effects of current treatments with beta-blockers or calcium antagonists on the clinical outcome of acute myocardial infarction (MI), enzymatically estimated infarct sizes, circulatory arrests from ventricular tachyarrhythmias, ventricular tachycardia (VT)/ventricular fibrillation (VF), and in-hospital mortality were analyzed retrospectively from 7,922 citizens of Malm?, Sweden, hospitalized due to a first MI between 1973 and 1987. Of these patients, 296 were on treatment with calcium antagonists, 393 on treatment with a beta 1-selective beta-blocker, 482 with a nonselective beta-blocker, and 95 on combined treatment with beta-blockers and calcium antagonists at the time of admission to hospital. In a set of multivariate analyses including several clinical characteristics, patients on treatment with a nonselective beta-blocker had a significantly lower peak aspartate aminotransferase (ASAT; difference -0.70 mukat/l, 95% CL: -1.24 to -0.16), whereas no significant relations between peak ASAT and treatment with cardioselective beta-blockers or calcium antagonists were found. Treatment with cardioselective beta-blockers or calcium antagonists, in contrast to treatment with a nonselective beta-blocker, were significant predictors of the occurrence of circulatory arrests from VT/VF. The relative risk of VT/VF in patients on cardioselective beta-blockers was 1.51 (95% CI: 1.12-2.03), and in patients on calcium antagonists 1.44 (95% CI: 1.03-2.02). None of the treatments were significantly associated with in-hospital mortality. In patients on beta-blockers or calcium antagonists when suffering their first MI, nonselective beta-blockade may reduce infarct size. Treatment with beta-blockers or calcium antagonists identified patients with an increased risk of circulatory arrests from VT/VF, but neither of the treatments were significantly associated with in-hospital mortality. We suggest that only minor differences exist between the effects of chronic treatment with beta-blockers and calcium antagonists on the outcome of an acute MI.     

Exercise-induced polymorphic ventricular tachycardia in adults without structural heart disease

Patients with catecholaminergic polymorphic ventricular tachycardia present at a young age with exercise-induced ventricular arrhythmias (VAs) and may have a positive family history. We describe 8 patients who presented with exercise-induced symptoms as adults, have a negative family history, and responded to beta-blocker therapy. The study evaluated exercise treadmill electrocardiographic data from patients referred for exercise-induced VA. Inclusion criteria consisted of development of bidirectional, pleomorphic, or polymorphic ventricular tachycardia with exercise, adult age at first onset, negative family history, and no evidence of structural heart disease. We correlated VA configurations with respect to heart rate before and after beta-blocker therapy. Patients displayed a pattern of increasing ventricular complexity with increasing heart rate. The appropriate beta blocker (n = 7) or calcium channel blocker (n = 1) was defined as the dose that resulted in control of symptoms. Three patients showed suppression of VA with sinus tachycardia at peak heart rate. Six patients had decreased VA defined as absence of higher complexity arrhythmias. With drug therapy, average heart rate associated with premature ventricular complex couplets/triplets increased, whereas duration and complexity of premature ventricular complexes decreased. One patient had an automatic implantable cardiac defibrillator placed but has had no discharges from the device since starting the appropriate beta blocker. In conclusion, these patients appear to respond well to beta-blocker or calcium channel blocker therapy with decreased ectopic complexity and an increased heart rate threshold for inducing VA.     

Low doses of intravenous epinephrine for refractory sustained monomorphic ventricular tachycardia

We report three cases of sustained monomorphic ventricular tachycardia(VT) in the setting of coronary artery disease,resistant to beta-blockers in two patients and to amiodarone in all,successfully terminated by low doses of intravenous(IV) epinephrine.VT was the first manifestation of coronary artery disease in one patient,whereas the other two patients had a previous history of myocardial infarction and were recipients of an implantable cardioverter-defibrillator(ICD).One of these two patients experienced an arrhythmic storm.All had hemodynamic instability at the time of epinephrine administration.A single slow administration of IV epinephrine(0.5 to 1 mg administered over 30 to 60 s) restored sinus rhythm after 30-90 s with only minor side effects.In the ICD patient with recurrent VT and several cardioversions due to transformation of VT to ventricular fibrillation,epinephrine injection led to the avoidance of further shocks.Although potentially harmful,low doses of IV epinephrine used alone or in combination with beta-blocker treatment and electrical cardioversion may be an alternative effective therapy for sustained monomorphic VT refractory to amiodarone.The role of epinephrine in the termination of VT should be studied further,especially in patients pre-treated with amiodarone in combination with beta-blockers.     

T Wave Pacing Inducing Electrical Storm and Multiple Shocks in an ICD-Recipient: A Novel Complication of the Automatic Gain Control Function

Implantable cardioverter-defibrillator (ICD) is highly effective in treating life-threatening ventricular arrhythmias, but it can also have proarrhythmic effect in some cases. We report the case of a 72 years old patient with an ischemic cardiomyopathy in whom an ICD was implanted for a poorly tolerated ventricular tachycardia (Profiles MD—Ventritex). Forty-eight hours after implantation, the patient suddenly received 15 successive shocks. ECG tracings and intracardiac EGM showed the presence of several VT episodes, all induced by the antibradycardia pacing of the ICD: the automatic gain control function of the device failed to detect ventricular premature beats in this patient, leading to a bradycardia pacing falling on the T wave and inducing multiple VTs and shocks.     

Implantable cardioverter defibrillator shocks from ventricular tachyarrhythmias in patients with ischemic heart disease: Preventative measures,shortcomings, cost-effectiveness,and global practice perspectives

Implantable cardioverter defibrillators (ICDs) have proven to be life-saving devices in patients with ischemic cardiomyopathy (ICM) who are prone to develop ventricular tachycardia (VT) and fibrillation (VF). Antiarrhythmic drugs (AADs) are commonly prescribed in many such patients with ICDs to treat and prevent different forms of arrhythmias in clinical practice. When these patients experience recurrent monomorphic VT despite chronic AADs therapy, or when AAD therapy is contraindicated or not tolerated, and VT storm is refractory to AAD therapy, catheter ablation constitute guideline-based class I indication of treatment. However, what should be the most appropriate strategy to prevent first ICD shock or subsequent multiple shocks from VT/VF in patients with ICM who undergo ICD implantation without prior incidence of cardiac arrest, remains debatable. The purpose of this review is to discuss preventative aspects of ICD shocks for VT and the shortcomings of these measures along with the cost-effectiveness and global perspectives based on the current knowledge of the topic.     

Randomized controlled study of detection enhancements versus rate-only detection to prevent inappropriate therapy in a dual-chamber implantable cardioverter-defibrillator

OBJECTIVES: The purpose of this study was to compare rate-only detection to enhanced detection in a dual-chamber implantable cardioverter-defibrillator (ICD), to discriminate ventricular tachycardia from supraventricular tachycardia. BACKGROUND: ICDs are highly effective in treating ventricular tachycardia (VT) or ventricular fibrillation (VF). However, they frequently deliver inappropriate therapy during supraventricular tachycardia (SVT). METHODS: We conducted a randomized clinical trial of detection enhancements in a dual-chamber ICD compared to control (rate-only) detection to discriminate VT from SVT. Detection enhancements included a specific standardized protocol identical for all patients for programming rate stability, sudden onset, atrial-to-ventricular relationship (sudden onset = 9% and rate stability = 10 ms; V > A "on"), and "sustained rate duration" (3 minutes). The primary endpoint was the time to first inappropriate therapy classified by a blinded events committee. RESULTS: One hundred forty-nine patients had a history of sustained VT or VF. Mean age (+/- SD) was 60 +/- 13 years; 83% were male, and mean ejection fraction was 35 +/- 15%. Control (n = 70) and "enhanced" (n = 79) groups did not differ with regard to age, sex, ejection fraction, or primary arrhythmia. The proportion of patients free of inappropriate therapy over time was significantly higher in the enhanced versus the control group (hazard ratio = 0.47, P = .011). High-energy shocks were reduced from 0.58 +/- 4.23 shocks/patient/month in the control group to 0.04 +/- 0.15 shocks/patient/month in the enhanced group (P = .0425). No patient programmed per protocol failed to receive therapy for VT detected by the ICD (422 VT episodes). CONCLUSIONS: Standardized programming in a dual-chamber ICD leads to a significant and clinically important reduction in inappropriate therapies compared to rate-only detection and does not compromise safety with respect to appropriate treatment of VT.     

Prevalence and clinical background of exercise-induced ventricular tachycardia during exercise testing

OBJECTIVES: This study assessed the prevalence and clinical background of exercise-induced ventricular tachycardia during exercise testing. METHODS: Complications during exercise testing were reviewed in 25,075 consecutive patients, 14,037 men and 11,038 women, who underwent a total of 47,656 maximal treadmill or bicycle exercise tests between April 1985 and March 1999. The mean age of the patients was 53.3 +/- 8.8 (mean +/- SD) years. Non-sustained ventricular tachycardia was defined as 8 or more consecutive ventricular ectopic beats at > 100 beats/min. A total of 126 patients undergoing exercise testing to evaluate the efficacy of pharmacotherapy for ventricular tachycardia were excluded. RESULTS: The major reasons for the exercise test were chest pain (27.0%) and screening (20.3%). Twenty patients (0.08%) had exercise-induced ventricular tachycardia. Six patients had ischemic heart disease, two had cardiomyopathy, five had other cardiac diseases, and seven patients showed no clinical evidence of heart disease. The incidence of ventricular tachycardia in patients with cardiomyopathy (2/109) was higher than in other patients, but the number of patients with ventricular tachycardia was small. Ventricular tachycardia was documented at heart rates of more than 80% of predicted maximal heart rate in 12 of the 20 patients. CONCLUSIONS: These results suggest that the exercise testing can be done safely when the end-point criteria are properly applied.     

Antiarrhythmic effects of oral indecainide in patients with ventricular tachyarrhythmias

In order to assess the efficacy and safety of oral indecainide in patients with serious ventricular arrhythmias we studied 11 patients with high-grade ventricular ectopy and ventricular tachycardia (VT) which were refractory to therapy with at least one standard antiarrhythmic drug. Spontaneous arrhythmias were quantitated by 24-h Holter monitor before and during therapy with indecainide. Spontaneous VT was sustained in 4 patients and nonsustained in 7. Ten patients underwent baseline electrophysiologic study (EPS) and VT was induced in 9. The mean ejection fraction was 25 +/- 14%. Indecainide was given orally at a dose of 211 +/- 118 mg/day. The frequency of ventricular premature beats (VPBs) was significantly (greater than 85%) decreased in 90% of patients, while ventricular couplets frequency decreased in 78%. Spontaneous VT was abolished in 5 of 11 (45%). Sustained VT was induced in 5 of 7 (71%) patients who underwent follow-up EPS. The QRS duration was significantly prolonged during therapy (0.13 +/- 0.04 s) compared to control (0.10 +/- 0.02 s). The PR, QTc, and JTc intervals were not significantly changed. Indecainide was well tolerated, but 2 patients died of ventricular tachyarrhythmias while receiving the drug. Indecainide suppressed VPBs in a high percentage of patients, but was much less successful in controlling VT. Caution is necessary when using this drug because of its potential for exacerbation of arrhythmia.