Relation of atrial refractoriness to upper and lower limits of vulnerability for atrial fibrillation/flutter following implantable ventricular defibrillator shocks.

BACKGROUND: Implantable ventricular cardioverter defibrillator (ICD) shocks can cause atrial fibrillation/flutter (AF). This study investigated the pathogenesis of AF after ICD shocks in a canine model. METHODS AND RESULTS: The study was conducted in 8 dogs. In 5 dogs (group 1), truncated exponential (8 ms, 78% tilt) monophasic and biphasic shocks were delivered through a bipolar epicardial (patch) or endocardial lead. After the last S1 of atrial pacing at a cycle length of 350 ms, shocks of 0.1 to 7.6 A (0.005 to 27.7 J) were delivered, timed to the atrial effective refractory period (AERP). Ventricular defibrillation thresholds were also determined. In 3 dogs (group 2), the effect of the open versus closed chest technique on AF induction was tested in the endocardial biphasic shock configuration. AF was induced in all 8 dogs and in all waveforms and configurations. Mean AF duration was 11.5+/-6 s, with a mean ventricular rate of 184+/-37 bpm. Ventricular shocks could induce AF only if they were timed between an AERP of -60 to 40 ms, -40 to 60 ms, -40 to 60 ms, and -20 to 60 ms in the epicardial monophasic, epicardial biphasic, endocardial monophasic, and endocardial biphasic configurations, respectively. The mean+/-SD of the upper limit of vulnerability (ULV) for AF induction (in J) was 5. 2+/-0.6, 3.5+/-0.4, 5.2+/-1.2, and 2.5+/-0.1 for the epicardial monophasic, epicardial biphasic, endocardial monophasic, and endocardial biphasic configurations, respectively (P<0.05). The lower limit of vulnerability (LLV) was 0.8+/-0.1, 0.8+/-0.1, 0.9+/-0, and 0.6+/-0 for the epicardial monophasic, epicardial biphasic, endocardial monophasic, and endocardial biphasic configurations, respectively (P=NS). The ventricular defibrillation threshold (in J) for all wave forms and configurations was higher than the ULV (P<0. 05). CONCLUSIONS: (1) An atrial LLV and ULV exist for ventricular ICD shock-induced AF; (2) the shock-induced AF is related to both shock intensity and its timing to AERP; and (3) avoiding this atrial window of vulnerability may minimize the risk of post-ICD shock AF.

Comparison of programmed electrical stimulation and ambulatory electrocardiographic (Holter) monitoring in the management of ventricular tachycardia and ventricular fibrillation.

Forty-four patients with primary ventricular fibrillation or recurrent ventricular tachycardia were stabilized on an antiarrhythmic drug regimen before electrophysiologic study and 24 to 72 hours of ambulatory electrocardiographic monitoring were performed. The long-term predictive value of these two tests was then compared retrospectively for a 12 to 32 month (mean 18) follow-up period, during which all patients continued receiving the same antiarrhythmic drug regimen. Electrophysiologic testing induced ventricular tachycardia (greater than or equal to 3 beats) in 26 patients; 23 had a poor clinical outcome (positive predictive value 88%), defined as sudden death or sustained ventricular tachycardia. In 18 patients with a negative electrophysiologic test, only 1 had a poor clinical outcome (negative predictive value 94%). Ambulatory electrocardiographic monitoring accurately predicted outcome in 7 of 10 patients with a positive recording (positive predictive value 70%), defined as three or more consecutive ventricular extrasystoles, and in 17 of 34 patients with negative ambulatory monitor recordings (negative predictive value 50%). The long-term predictive accuracy of the electrophysiologic study was significantly higher than that of the ambulatory electrocardiographic monitor (p less than 0.001). Electrophysiologic studies offer advantages over ambulatory electrocardiographic monitoring in this high risk patient group, providing a high degree of accuracy in predicting the long-term clinical response to antiarrhythmic drugs for at least 18 months.

Amiodarone pulmonary toxicity: early changes in pulmonary function tests during amiodarone rechallenge.

Amiodarone is an investigational antiarrhythmic agent known to cause pulmonary toxicity. This report describes two patients with previous amiodarone pulmonary toxicity and complete resolution who at rechallenge 5 to 6 months later developed within 2 weeks of therapy a significant reduction in lung diffusion capacity before overt clinical toxicity occurred. This suggests that toxicity may present early with reduction in diffusion capacity and that such changes may warrant the need to alter treatment.

Amiodarone in the treatment of life-threatening ventricular tachycardia: role of Holter monitoring in predicting long-term clinical efficacy.

Forty-two patients with refractory, recurrent life-threatening ventricular tachycardia and spontaneous ventricular tachycardia (greater than or equal to 3 beats, heart rate greater than 100 beats/min) on baseline 24 hour Holter recording were treated with amiodarone. After 1 week of amiodarone therapy and during the follow-up period (22 +/- 11 months, mean +/- SD), patients had serial 24 hour Holter recordings (10.6 +/- 3.8 per patient). Twenty-four hour, 48 hour or 72 hour Holter monitoring was performed during the second week of therapy. Ventricular tachycardia was suppressed on all follow-up serial Holter recordings in 17 patients (40%). Ventricular tachycardia was suppressed in 34 (81%) of 42 patients with 24 hour Holter recordings, 21 (72%) of 29 patients with 48 hour recordings and 20 (69%) of 29 patients with 72 hour recordings during the second week of therapy. At follow-up 24 patients (57%) were free of clinical arrhythmic events (Sustained ventricular tachycardia or sudden death). The sensitivity, specificity, positive and negative predictive values and predictive accuracy of ventricular tachycardia on 24, 48 and 72 hour Holter recordings during the second week of therapy for predicting subsequent events were analyzed. The positive and negative predictive values were 100 and 71% for 24 hour Holter recordings, 88 and 71% for 48 hour recordings and 89 and 75% for 72 hour recordings. Overall predictive accuracy was 76, 76 and 79%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The utility of aprindine blood levels in the management of ventricular arrhythmias.

Sixty-four patients with a history of ventricular tachycardia and ventricular fibrillation refractory to conventional therapy received aprindine to abolish recurrent episodes of symptomatic ventricular tachycardia. Fifty-six patients became asymptomatic and were followed up for a mean period of 23 months. Aprindine dose was adjusted to minimize adverse reactions but still control arrhythmia. Survival analysis was performed for the group with aprindine levels greater than 1.5 micrograms/ml and the group with levels of 1.5 micrograms/ml or less. At the end of the study, 65% of the patients with a high level were alive and asymptomatic as compared with only 35% of the patients with a low level (p less than 0.036). In patients at risk of recurrent sudden cardiac death, high aprindine levels maintained after abolition of symptomatic ventricular tachycardia were associated with improved survival.

The automatic implantable cardioverter-defibrillator. Long-term clinical experience and outcome at a hospital without an open-heart surgery program.

From November 1982 through April 1989, 111 patients with refractory sustained ventricular tachycardia/fibrillation had the automatic cardioverter-defibrillator implanted at our institution, the first community hospital involved in implantation of such a device. We have reviewed our long-term clinical experience to assess the feasibility, learning curve, and efficacy of device implantation in a facility with cardiac electrophysiology expertise but without open-heart surgery facilities. All patients were considered inoperable or at high risk for other concomitant surgery. Eighty-six patients (77%) underwent uneventful implantation. Nine patients (8%) died prior to hospital discharge. Operative mortality declined from 10.9% to 5.4% during the first half (55 patients; November 1982 through September 1986) and second half (56 patients; October 1986 through April 1989) of the experience. Other postoperative complications occurred in 16 patients (14%), 12 of whom experienced complications during the first half of the experience. At 22 +/- 20 (mean +/- SD) months' follow-up, 78 (76%) of 102 patients discharged were alive, and 24 patients (24%) had died. Fifty patients (49%) had experienced at least one automatic cardioverter-defibrillator discharge associated with hypotensive symptoms. The actuarial incidence of sudden death at 1, 2, and 3 years was 1.2%, 5.5%, and 6.2%, respectively. We concluded that the automatic implantable cardioverter-defibrillator is an effective therapy for refractory ventricular tachycardia/fibrillation and that device implantation at community hospitals with an experienced cardiac electrophysiology team is both feasible and practical.

Dose-ranging studies of clofilium, an antiarrhythmic quaternary ammonium.

Clofilium, a new quaternary ammonium antiarrhythmic without apparent ganglion-blocking effect, was evaluated in 25 patients, 22 with a history of ventricular arrhythmias and three with paroxysmal supraventricular arrhythmias. The study, including programmed atrial and ventricular stimulation, was carried out before and after infusion of 20 to 240 micrograms/kg IV as a single dose. Continuous Holter monitoring was carried out the day before the study through the fourth day after study, and laboratory parameters were monitored for up to 2 wk. There were no changes in intra-atrial and intraventricular conduction times or in AH or HV intervals. There were increases in QT interval, atrial effective refractory period, and ventricular refractory period. The atrioventricular nodal effective refractory period was unchanged. No side effects were noted, nor were changes in blood pressure or laboratory parameters. Monitoring revealed no change in frequency of premature ventricular complexes between the 24 hr before drug infusion and the 96 hr thereafter. In one patient refractoriness of the His-Purkinje system was increased and in two patients atrial fibrillation converted to sinus rhythm after clofilium. Three patients had sustained ventricular tachycardia with programmed stimulation before clofilium infusion; none had more than three repetitive ventricular responses after it. Clofilium increases atrial and ventricular effective refractory period without changing conduction time and, despite no apparent change in premature ventricular complex frequency, it can abolish the ability to induce ventricular tachycardia by programmed stimulation and is also well tolerated.

Suppression of complex ventricular arrhythmias by oral flecainide.

The effectiveness and safety of oral flecainide for suppression of complex ventricular arrhythmias was tested in nine patients in a short-term (4 wk), single-blind, placebo-controlled experiment. The prevalence of multiform premature ventricular complexes (PVCs), couplets and nonsustained ventricular tachycardia (VT) (less than 3 PVCs at rate less than 100/min) was determined by 48-hr Holter monitoring on placebo and flecainide (200 to 300 mg b.i.d.) therapy. Multiform PVCs/hr were reduced by 96% in eight of nine patients (P less than 0.001). Couplets per 24-hr period were suppressed entirely in six patients (P less than 0.001). Couplets per 24-hr period were suppressed entirely in six patients (P less than 0.001) and reduced by 92% in the remaining two patients. VT runs per 24 hr were abolished in six patients (P less than 0.02) and reduced by 91% in one. As a group the frequency of PVCs per hour, couplets per 24 hr and VT per 24 hr was reduced by 96% (P less than 0.01) over than in the preceding placebo period. Flecainide (P less than 0.02) slowed heart rate by 10% and prolonged PR, QRS, and QTc intervals by 31%, 47% and 6%. No hematologic, hepatic, or renal abnormalities were found. Side effects were mild, transient, and central nervous system related; blurring of vision was the most frequent effect and was reported in four patients.

Ventricular ectopy: etiology, evaluation, and therapy.

Ventricular ectopy occurs commonly. Its significance is related to the degree of complexity and the associated cardiac substrate. Coronary artery disease is the most frequent underlying cause, followed by cardiomyopathy and valvular disease. Symptomatic ventricular arrhythmias require treatment, whereas benign simple ventricular ectopy does not; however, the treatment of asymptomatic high-grade ventricular ectopy remains controversial. Therapy first must be directed toward the cardiac disease. Evaluation of the patient includes Holter monitoring, echocardiography, radionuclide studies, exercise testing, cardiac catheterization, and electrophysiologic testing. Programmed stimulation is useful in the diagnosis and prognosis of ventricular tachycardia, as well as in the evaluation of drug regimen efficacy. After treatment of ischemia and/or failure, specific antiarrhythmic agents, conventional and investigational, alone or in combination, are systematically selected. Should medical therapy alone be insufficient, consideration is given to surgical procedures such as subendocardial resection or ventriculotomy, often in combination with bypass grafting, aneurysmectomy, or valvular replacement. Electronic devices, including pacemakers or automatic internal defibrillators, may also be useful in certain selected cases. Suggested guidelines are proposed for a standardized approach, although therapy for each patient must still be individualized.

Refractory symptomatic ventricular tachycardia and ventricular fibrillation in elderly patients.

The problem of refractory life-threatening ventricular tachyarrhythmias in elderly patients has not been previously studied. To determine if clinical, anatomic, or electrophysiologic variables and prognosis are significantly different in elderly subjects, 49 elderly (68 to 84 years) and 44 younger (44 to 53 years) survivors of refractory symptomatic ventricular tachycardia and/or ventricular fibrillation secondary to coronary artery disease were studied. Elderly patients displayed more extensive anatomic coronary artery disease, with 80 percent having three-vessel disease in comparison with 30 percent of the younger patients (p less than 0.001). Prior myocardial infarction, heart failure, and cardiomegaly were more common in the elderly group (p less than 0.01, p less than 0.001, and p less than 0.034, respectively), whereas angina was more common in the younger group (p less than 0.001). In 55 percent of the elderly patients and 58 percent of the younger patients, electrophysiologic testing demonstrated inducible sustained ventricular tachycardia that required treatment with an investigative antiarrhythmic drug and/or cardiac surgery, including implantation of an automatic defibrillator. Elderly patients tolerated aggressive evaluation as well as did younger patients, and despite the difference in clinical and anatomic findings, long-term survival curves were similar, although the probability of survival at 20 months was 62 percent in the elderly and 80 percent in the younger patients. This difference in early survival is explained by eight surgical deaths in the elderly group, compared with two in the younger group.

Assessment of the site of ventricular activation by Fourier analysis of gated blood-pool studies.

We studied the use of first-harmonic Fourier analysis of gated blood-pool images to assess the site of ventricular activation in a group of 12 patients undergoing electrophysiologic pacing studies. We acquired gated blood-pool studies during pacing at up to four sites at each of two different rates. A total of 50 studies were made. At a pacing rate of 100 beats/min, when the pacing electrode was at the right-ventricular apex, 9/13 times the Fourier activation site agreed; at the right-ventricular outflow tract, 7/8; at the anterolateral left-ventricular wall, 4/4. When the Fourier activation site was at the right-ventricular apex, 9/9 times the pacing electrode was there; at the right-ventricular outflow tract, 7/10; in the left ventricle, 4/4. Fourier analysis of gated blood-pool studies can help identify the site of ventricular activation but is not sufficiently accurate to fully replace endocardial mapping.

Relation of time course of plasma nitroglycerin levels to echocardiographic, arterial pressure and heart rate changes after sublingual administration of nitroglycerin.

Despite the widespread use of nitroglycerin, a relation between plasma nitroglycerin concentrations and the associated cardiovascular effects has not been well established. It was hypothesized that nitroglycerin levels may help predict the hemodynamic responses. With use of a recently developed nitroglycerin assay technique, the relation between the time course of plasma nitroglycerin levels and echocardiographic changes after sublingual administration of 0.6 mg of the drug was evaluated in 12 normal volunteers. Mean plasma nitroglycerin levels were maximal at 2 (1.1 +/- 0.3 ng/ml) and 5 (1.4 +/- 0.6 ng/ml) minutes, when the changes in mean heart rate (+17 +/- 7 and +12 +/- 3 min-1) and decreases in echocardiographic left ventricular diastolic (-4.2 +/- 0.8 mm at 5 minutes) and systolic (-3.1 +/- 0.6 mm at 5 minutes) dimensions were also maximal. Parallel changes were noted in left atrial dimension, ventricular velocity of circumferential fiber shortening and systolic blood pressure, but not in diastolic blood pressure. These findings demonstrate the existence of a close relation between plasma nitroglycerin levels and variables that reflect the known responses to this drug.

Nonsustained ventricular tachycardia during programmed ventricular stimulation: criteria for a positive test.

Controversy persists among groups carrying out programmed ventricular stimulation (PVS) as to which criteria should be used to define a positive test. To examine this question, the results of PVS carried out in 50 patients with documented sustained ventricular tachycardia (VT) or ventricular fibrillation were retrospectively analyzed. All patients underwent serial PVS using single and double extrastimuli and ventricular burst pacing in the right ventricle and, when necessary, the left ventricle, with sustained VT elicited during the control study in each patient. Antiarrhythmic drugs were then administered, with therapy tailored to both PVS result and ambulatory Holter monitoring, when possible. All patients were maintained and followed on the same drugs and dosages as at the time of predischarge PVS. After mean 20 months follow-up, 28 patients either died suddenly (8 patients) or had documented sustained VT (20 patients). The ability to induce nonsustained or sustained VT on predischarge PVS was associated with a significantly higher likelihood of subsequent sudden death or VT recurrence than if VT could not be induced (p less than 0.001). In addition, using the criterion of 5 or more beats of induced VT to define a positive study maximized the predictive value of PVS and provided a significantly higher predictive accuracy than if only sustained VT were used to define a positive study.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic assessment of survivors of ventricular tachycardia and ventricular fibrillation with ambulatory monitoring.

The ability to assess prognosis in patients with serious ventricular arrhythmias treated with antiarrhythmic drugs by the degree of complexity on the 24-hour ambulatory electrocardiogram was evaluated in 59 survivors of ventricular tachycardia (VT) and ventricular fibrillation. After conventional therapy had failed, patients were treated with investigational drugs until symptomatic VT was abolished. A Holter monitor recording, obtained once the therapeutic regimen was established, was graded for the presence or absence of asymptomatic VT. Fifty-two patients were asymptomatic at discharge and were followed for 700 days. Of 44 patients followed for 1 year, none had recurrent syncope or died if asymptomatic VT was absent at 1 month (p less than 0.002). After 700 days, 27 patients (82%) without asymptomatic VT at 1 month were doing well, compared with 11 patients (58%) with asymptomatic VT at 1 month (p less than 0.002). In patients at risk for sudden cardiac arrest, early abolition of asymptomatic VT on ambulatory monitoring can be used to predict a good long-term clinical response.

Mechanism of the repetitive ventricular response in man.

The electrophysiologic characteristics of the repetitive ventricular response that followed an electrically induced single premature ventricular complex were evaluated to determine its mechanism during atrial pacing or sinus rhythm in 30 patients. Seven patients had preexisting bundle branch block. His bundle or right bundle branch deflections did not precede the repetitive complex in 29 of the 30 patients, which implies that the proximal His-Purkinje system was not involved in the reentry circuit. In 24 of 30 patients the QRS axis ot the repetitive complex was divergent 45 degrees or more from the stimulated complex. In 22 of 30 patients the reprtitive complex had a right bundle branch block configuration. In 14 of 18 patients with two or more repetitive complexes, the QRS pattern changed from beat to beat, which implies that either the reentry pathway or conduction was changing. Thus, the repetitive ventricular response, which can be associated with clinically important ventricular arrhythmias, probably represents intraventricular rather than proximal His-Purkinje system reentry.

Prolongation of cardiac conduction times by intravenous aprindine in man.

The acute electrophysiologic effects of intravenous aprindine were evaluated in 48 patients to assess the effect on conduction times and refractoriness in patients with severe cardiac disease and arrhythmias. The patients had not responded to conventional antiarrhythmic medications or had been unable to tolerate effective doses of conventional medications because of side effects. Eleven patients had an abnormal H-V interval, 9 had prolonged QRS duration and 22 had evidence of severe left ventricular dysfunction. Aprindine prolonged conduction transiently in the atria, the atrioventricular (A-V) node, the His-Purkinje system and the ventricles. The refractory times of the atria, the A-V node and the ventricles increased insignificantly, both functionally and statistically. Atrioventricular block did not develop in any patient, and side effects were minor. Thus, aprindine can be safely administered intravenously (10 to 15 mg/min) to severely ill patients with arrhythmias that are refractory to other medications even in the presence of underlying conduction system and myocardial disease.

Suppression of the repetitive ventricular response: an index of long-term antiarrhythmic effectiveness of aprindine for ventricular tachycardia in man.

The repetitive ventricular response, defined as the production of two or more ventricular premature complexes in response to a single ventricular pacing stimulus, is common in patients with serious ventricular arrhythmias. Twenty-seven patients with refractory ventricular tachycardia were studied to determine whether acute suppression of the repetitive ventricular response by aprindine predicts long-term effectiveness of this agent. Twenty-three of the 27 patients had the repetitive ventricular response before intravenous administration of aprindine, whereas only 6 had the response after aprindine. All patients were maintained on a regimen of oral aprindine and evaluated repeatedly for a mean of 12 months. Twenty of the 21 patients who had no repetitive ventricular response after intravenous aprindine manifested clinical improvement compared with only 1 of the 6 in whom the repetitive response was present after aprindine (P less than 0.0005). Aprindine is a useful agent in refractory ventricular tachycardia, and the absence of the repetitive ventricular response after its intravenous administration predicts long-term clinical responsiveness to the oral form.

Effect of electrical activation site on left ventricular performance in ventricular tachycardia patients with coronary heart disease.

Some patients with ventricular tachycardia (VT) remain virtually asymptomatic, whereas others have syncope despite similar VT rates. The role of ventricular activation site on left ventricular (LV) function was examined in 10 patients undergoing electrophysiologic evaluation for recurrent ventricular arrhythmias. Radionuclide ventriculograms were acquired to calculate LV volumes and aortic or LV pressure was measured during right atrial and right ventricular (RV) pacing. RV apical pacing resulted in end-diastolic volumes similar to those achieved with right atrial pacing (171 +/- 27 vs 175 +/- 19 ml), whereas RV outflow tract pacing showed a trend toward lower volumes (168 +/- 32 vs 177 +/- 33 ml). Comparison between RV apical and RV outflow tract pacing showed that apical activation resulted in higher end-diastolic volumes (216 +/- 26 vs 194 +/- 22 ml, p = 0.020), end-systolic volumes (175 +/- 25 vs 158 +/- 20 ml, p = 0.041), stroke volumes (42 +/- 4 vs 36 +/- 6 ml, p = 0.046), peak rates of LV ejection (309 +/- 57 vs 245 +/- 40 ml/s, p = 0.034) and peak rates normalized for differences in end-diastolic volume (1.5 +/- 0.3 vs 1.3 +/- 0.3; p = 0.047) without a significant increase in peak pressures (131 +/- 12 vs 127 +/- 14 mm Hg, p greater than 0.30) or ejection fractions (24 +/- 5 vs 22 +/- 4%, p = 0.187). These changes were accompanied by an increase in LV/RV stroke count ratios during RV apical vs RV outflow tract pacing (1.6 +/- 0.2 vs 1.2 +/- 0.2, p = 0.030), suggesting the development of mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Myocardial prostaglandin E release by nitroglycerin and modification by indomethacin.

In open chest dogs, studies were made of the effects of intravenous trinitroglycerin (10 micrograms/kg per min) on circumflex arterial coronary blood flow, coronary vascular resistance, systemic arterial pressure and myocardial prostaglandin E production before and after indomethacin (n = 9) or indomethacin vehicle (n = 5). During a 30 minute trinitroglycerin infusion, coronary sinus prostaglandin E concentration increased significantly (approximately +41 percent, p less than 0.01) without significant changes in left atrial prostaglandin E concentration. After indomethacin (5 mg/kg), but not indomethacin vehicle alone, a second trinitroglycerin infusion (10 micrograms/kg per min) produced a significantly smaller decrease in coronary vascular resistance (p less than 0.05) and systemic blood pressure (p less than 0.01) and no increase in coronary sinus prostaglandin E (p less than 0.001) by comparison with control values. The heart rate response to trinitroglycerin was significantly greater (p less than 0.05) after than before indomethacin. This study suggests that the mechanism of action of trinitroglycerin may be at least partially mediated through the prostaglandin system.

Evaluation of flecainide acetate in the management of patients at high risk of sudden cardiac death.

The clinical effectiveness of flecainide acetate was evaluated in 36 patients (29 male and 7 female, average age 56 years) in whom therapy with previous antiarrhythmic agents had failed. All patients had documented ventricular tachycardia on Holter electrocardiographic recording and 31 of 36 (86%) had had syncope or required cardiopulmonary resuscitation, or both. Angiographic findings demonstrated significant coronary artery disease in 22 (61%) and primary left ventricular dysfunction in 14 (39%), with a left ventricular ejection of 0.39 +/- 0.4. Patients were treated with an average flecainide dose of 302 +/- 76 mg/day. The follow-up time was 101 +/- 156 days. Thirty-two of 36 patients (89%) had complete elimination of ventricular tachycardia from Holter monitoring and only 2 patients had flecainide discontinued because of noncardiac side effects (numbness, blurred vision and ataxia). However, the drug was subsequently discontinued in 5 patients because of cardiac side effects (proarrhythmic effect in 2, sinus bradycardia in 1, complete atrioventricular block in 1 and new left bundle branch block in 1) and 10 patients died during flecainide therapy (1 with cerebral stroke, 3 with congestive heart failure and 6 with incessant ventricular tachycardia). A comparison of the general cardiac features of those who died with those who did not revealed a significantly lower ejection fraction (0.24 +/- 0.1 vs 0.45 +/- 0.1, p less than 0.05) and a significantly higher flecainide dose (350 +/- 85 versus 276 +/- 59 mg/day, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)