Class Ic Antiarrhythmic Agent Research Articles

An electrophysiological comparison of a novel class Ic antiarrhythmic agent, NIK‐244 (ethacizin) and flecainide in canine ventricular muscle

1. Electrophysiological effects of NIK-244 (ethacizin), a novel class I antiarrhythmic drug, were compared with flecainide in canine ventricular muscle by use of conventional microelectrode techniques. 2. At concentrations of 10(-6) M or higher, NIK-244 depressed the maximum rate of rise of depolarization (Vmax) significantly in a concentration-dependent manner. Also, the resting potential was depolarized at 10(-5) M. NIK-244 did not have any effect on the other action potential parameters or on the effective refractory period. 3. Flecainide significantly decreased Vmax at 3 x 10(-6) M or higher and the resting potential was depolarized at 10(-5) M. Like NIK-244, flecainide did not affect other action potential parameters. 4. NIK-244 and flecainide caused a use-dependent block of Vmax, and the rates of onset of inhibition at 3 Hz stimulation were 0.014 +/- 0.002 AP-1 at 2 x 10(-6) M NIK-244 and 0.021 +/- 0.012 AP-1 at 10(-5) M flecainide. Under the same conditions, the time constants of the recovery from use-dependent block were 27.1 +/- 13.3 s and 12.2 +/- 2.5 s for NIK-244 and flecainide, respectively. 5. These results suggest that NIK-244, like flecainide, should be classified as a slow kinetic drug and as Ic.

Encainide

Encainide is a class IC antiarrhythmic agent having little or no effect on action-potential duration or maximum diastolic potential but decreasing the maximum rate of phase O depolarization as well as increasing atrial and ventricular effective refractory periods. In intact animals or humans, encainide increases the AH, PR, QRS, and H-V intervals while not affecting the sinus node cycle length or JT interval. QT interval increases only by the concomitant increase in the QRS interval. Encainide is metabolized to O-demethyl encainide (ODE) and 3-methoxy-ODE (MODE), both of which are also antiarrhythmics with similar pharmacology to encainide. Encainide and its metabolites have little negative inotropic activity and ancillary pharmacology. Consequently, encainide has little or no effect on hemodynamic variables in patients with either normal or compromised cardiac function. The drug is well tolerated, with side effects being mainly those associated with its local anesthetic activity such as blurred vision and dizziness. Encainide is particularly effective in patients with excessive premature ventricular complexes (PVCs) and less so in patients with sustained ventricular tachycardia (VT). Like all antiarrhythmics, encainide may aggravate or precipitate new arrhythmias (proarrhythmia). The overall incidence of proarrhythmia is about 10%, with less occurring in patients with PVCs and more in those with sustained VT; also, the incidence of proarrhythmia is higher in patients with underlying heart disease. Encainide is also effective for the treatment of supra-ventricular arrhythmias, including atrial fibrillation, PSVT (both PAF as well as reentry of the nodal or W-P-W type), and ectopic atrial tachycardia. Its dosage and role in antiarrhythmic therapy are discussed.

β-Adrenoceptor Blocking Activity of Diprafenone in Anesthetized Dogs

The effects of diprafenone, a new class Ic antiarrhythmic agent, on canine hemodynamics and cardiac membrane beta-receptor antagonist binding activity, were compared with those of propafenone and propranolol. Mongrel dogs (4-5/group) were anesthetized intravenously (i.v.) with pentobarbital sodium (35 mg/kg) and instrumented for measurement of aortic and coronary blood flows (AF, CBF), blood pressure (BP), and heart rate (HR). Isoproterenol (ISO) was administered as bolus injections before (0.01, 0.03, and 0.1 micrograms/kg, i.v.) and after (0.01-3 micrograms/kg, i.v.) infusions of diprafenone or propafenone (0.3, 1, and 3 mg/kg) or propranolol (0.03, 0.1, and 0.3 mg/kg, i.v.). The ability of the antiarrhythmic agents to displace [3H]dihydroalprenolol (DHA) binding from isolated cardiac ventricular membranes in vitro was also evaluated. Each antiarrhythmic agent blocked the HR and BP responses to ISO in a competitive manner and decreased the specific binding of DHA to cardiac ventricular membranes. Propranolol was 2 to 7 times more potent as a beta-receptor blocking agent than diprafenone, which was 6 times more potent than propafenone. The equilibrium dissociation constants (Ki) for displacement of DHA by propranolol, diprafenone, and propafenone were 2.7, 14.3, and 252 nM, respectively, and have the same rank order of potency for in vivo inhibition of BP and HR responses to ISO. Diprafenone has significant beta-adrenoceptor blocking activity which may contribute to its efficacy as an antiarrhythmic agent and allow its use in treatment of arrhythmias refractory to therapy with class I and class II agents alone.

Encainide and flecainide: Are they interchangeable?

Encainide and flecainide are two recently released class IC antiarrhythmic agents that have been reported to be highly effective for suppressing all forms of ventricular arrhythmias. Both drugs are potent blockers of the sodium channel and produce marked slowing of conduction within the His-Purkinje system and myocardium. To establish if the response to one agent predicts the response to the other, the antiarrhythmic effect of the two drugs was compared in a group of 18 patients with malignant ventricular arrhythmia. Fourteen patients had sustained ventricular tachycardia and four patients had ventricular fibrillation. The average ejection fraction of this group was 37%. All patients had a high density of spontaneous ventricular arrhythmia and were evaluated noninvasively. Both drugs significantly reduced all forms of spontaneous arrhythmia. By Holter monitoring criteria, the effect of the two drugs was concordant in 61% ( p = NS). By exercise criteria, the concordance rate was 50% ( p = NS). Overall, 12 patients (67%) responded to encainide and eight (44%) patients responded to flecainide ( p = NS). Only 10 of 18 (56%) patients had the same response to both agents ( p = NS). There was no significant difference in ejection fraction or in average daily dose of drug between responders and nonresponders. Thus despite their similar electrophysiologic profile, the clinical antiarrhythmic effect of these two agents was different. For the noninvasive management of patients the response to one agent should not be used to predict the response to the other.

An Interim Perspective on the Removal of Encainide and Flecainide from the Cardiac Arrhythmia Suppression Trial

The national heart, lung, and blood institute and the Food and Drug Administration (FDA) recently announced that the two currently marketed class IC antiarrhythmic agents, encainide and flecainide, have been removed from the Cardiac Arrhythmia Suppression Trial (CAST). The purpose of this article is to provide an interim perspective on the use of encainide and flecainide based on the limited information that is currently available about the CAST findings

Efficacy of intravenous propafenone for the acute management of atrial fibrillation

Propafenone is a new class IC antiarrhythmic agent that is potentially useful for the management of patients with atrial fibrillation (AF). Recent studies demonstrate that oral propafenone is effective for maintaining sinus rhythm after electrical conversion from AF. 1–3 Intravenous propafenone is effective in rapidly terminating supraventricular tachycardia due to reentrant mechanisms. 4,5 Recently, intravenous propafenone was also reported to be useful in the acute management of AF in patients after cardiac surgery. 6 The present study was undertaken to examine the efficacy and safety of intravenous propafenone in the acute management of AF in a less restricted patient population.

Electrophysiologic effects, efficacy and tolerance of class Ic antiarrhythmic agents in Wolff-Parkinson-White syndrome

After extensive evaluation in clinical investigation, the class Ic antiarrhythmic agents flecainide and encainide have recently been approved for the treatment of ventricular arrhythmias. Preliminary reports indicate that these drugs may be useful in the treatment of a variety of supraventricular tachycardias, including atrioventricular reciprocating tachycardia and atrial fibrillation in the setting of Wolff-Parkinson-White (WPW) syndrome. 1–5 This prospective study was undertaken to evaluate systematically the electrophysiologic effects, clinical efficacy and tolerance of flecainide and encainide in patients with the WPW syndrome.

Treatment of life-threatening ventricular tachycardia with encainide hydrochloride in patients with left ventricular dysfunction

Encainide, a newly released class IC antiarrhythmic agent, was studied in 193 patients with ventricular tachycardia (VT) and depressed left ventricular ejection fraction or important arrhythmia-related symptoms. Therapy was evaluated by 24-hour continuous Holter monitoring if patients had nonsustained VT or by electrophysiologic testing if they had sustained VT. Holter monitoring was used in 99 patients and electrophysiologic testing in 94 patients. At baseline the mean age, percent men, percent with coronary artery disease and mean ejection fraction in the 2 groups was 62 versus 58 years, 76 versus 72%, 62 versus 89%, and 27 versus 30%, respectively. In the Holter monitoring group, 71 of 99 (72%) responded with a significant reduction in VT (35% received 25 mg 3 times a day, 47% received 35 mg 3 times a day, 14% received 50 mg 3 times a day and 4% received 50 mg 4 times a day). Adverse cardiac effects in these patients included a 7% incidence of serious proarrhythmic events that were probably related to encainide and a 2% incidence of sick sinus syndrome. In this group no patient developed congestive heart failure that was clearly attributed to encainide. Using electrophysiologic testing, 14 of 94 (15%) had sustained VT rendered noninducible, whereas 18 of 94 (19%) additional patients had partial electro-physiologic response defined as a more tolerable, slower VT. Overall, 32 of 94 (34%) were believed to be effectively treated in this group and were treated with encainide long-term. In the population evaluated by electrophysiologic testing, serious proarrhythmic events occurred in 15 of 94 (16%) and 3% had sinus pauses. One patient had an increase in congestive heart failure symptoms probably related to encainide with an associated prolonged QRS interval to 150 ms. Thus, encainide appears to be an effective agent for the control of ventricular tachyarrhythmias without a significant incidence of congestive heart failure. Careful inhospital electrocardiographic monitoring is required to detect early proarrhythmic events in this population.

Efficacy and safety of class IC antiarrhythmic agents for the treatment of coexisting supraventricular and ventricular tachycardia

Thirty-three patients with concurrent supraventricular (SVT) and ventricular tachycardia (VT) were treated with class IC antiarrhythmic agents. Twenty-two patients had atrial fibrillation (17 with paroxysmal and 5 with chronic fibrillation), 1 patient had ectopic atrial tachycardia and 11 patients had reentrant paroxysmal SVT (8 with atrioventricular node reentrant tachycardia, 3 with atrioventricular reentrant tachycardia). Of 5 patients with Wolff-Parkinson-White syndrome, 2 had only atrial fibrillation. Six patients had sustained VT and 27 had nonsustained VT. Twenty-nine patients had organic heart disease (16 with coronary artery disease, 8 with cardiomyopathy and 5 with valvular heart disease) and 4 had primary electrical disease. The mean ejection fraction was 40 ± 14% (range 15 to 66%). The study population's arrhythmias were not controlled despite having received 2 to 5 (mean 3.1) previous drug trials. Eighteen patients were referred for treatment of SVT and 15 were referred for treatment of VT (mean symptom duration 107 months). Efficacy was determined in 13 of 33 patients with sustained SVT or VT by programmed electrical stimulation and in 20 of 33 by telemetry and 24-hour Holter response. Twenty-two flecainide and 15 encainide trials were conducted in the 33 patients. Four patients underwent trials with both drugs. Of 33 patients with coexisting SVT and VT, 15 (45%) were controlled with an IC agent alone and 3 continued therapy with an IC agent plus additional therapy (2 drugs, 1 antitachycardia pacing). During the follow-up period (mean 10.4 months), flecainide produced a complete response in 9 patients and encainide in 9 patients. SVT was not controlled in 7 patients and VT was not controlled in 7 patients. One patient had neither arrhythmia controlled. Atrial or ventricular proarrhythmia was seen in 9 of 33 patients (27%) (5 with ventricular and 4 with atrial arrhythmia). Noncardiac side effects were uncommon. Oral class IC agents may be effective therapy for some patients with coexisting VT and SVT of different mechanisms. Patients with such complex arrhythmias should be evaluated carefully because there is a potential for both atrial and ventricular proarrhythmia.

Myocardial protective effects of the class Ic antiarrhythmic agent flecainide

The class Ic antiarrhythmic agent flecainide has recently become available in this country for management of ventricular arrhythmias. The pharmacologic and electrophysiologic features of this class of drug--marked sodium channel blockade producing inhibition of phase 0 of the myocardial action potential, moderate blockade of slow inward (calcium) channels, and general lack of systemic toxicity--suggest that these agents may exert significant myocardial protective effects. This hypothesis was tested in isolated, perfused rat hearts subjected to 30 minutes of global normothermic ischemia followed by 30 minutes of reperfusion after pretreatment with (1) Krebs-Henseleit buffer (n = 7); (2) Krebs-Henseleit buffer with potassium adjusted to 20.9 mmol/L with potassium chloride (n = 10); and (3) Krebs-Henseleit buffer plus flecainide acetate 50 mg/L (0.12 mmol/L) (n = 11). Severity of ischemic injury was assessed by time to ischemic contracture: 9.9 +/- 1.3 (Krebs-Henseleit buffer), 18.4 +/- 1.1 (potassium chloride), and 25.4 +/- 1.0 (flecainide) minutes (mean +/- standard error of the mean) (p less than 0.05 among all groups). Functional recovery after ischemia and reperfusion was measured by developed pressure (expressed as percent of preischemic control): 19.6 +/- 5.4 (Krebs-Henseleit buffer), 70.8 +/- 3.2 (potassium chloride), and 67.3 +/- 2.7 (flecainide). These results suggest that class Ic agents afford significant myocardial protection from global normothermic ischemia.

Encainide: its electrophysiologic and antiarrhythmic effects, pharmacokinetics, and safety.

Encainide is a class IC antiarrhythmic agent that has been under clinical investigation for the last decade. Laboratory and clinical studies have demonstrated it to be a potent suppressor of ventricular extrasystoles. It is effective in approximately one-half of patients with malignant ventricular arrhythmias. The preliminary experience in patients with supraventricular arrhythmias indicates that the drug is particularly effective in arrhythmias associated with an accessory pathway. Side effects most commonly include blurred vision, nausea, heart block, and proarrhythmic effects. The hemodynamic effect of oral encainide are insignificant in patients with well-preserved left ventricular function. Despite minimal myocardial depression in patients with left ventricular dysfunction, there is the potential for worsening of heart failure. Encainide has a short half-life of 3 hours, but has 2 active metabolites with longer half-lives. No clinically significant drug interaction has been demonstrated with encainide therapy.

Use of diprafenone, a new potent propafenone-analogue, in acute experimental myocardial ischaemia and infarction.

Diprafenone (D) is a new class I c antiarrhythmic agent, structurally similar to propafenone. We assessed its antiarrhythmic and anti-fibrillatory effects during acute coronary occlusion and reperfusion and the underlying mechanisms of action by epicardial mapping of the conduction delay; also the effects of D on stimulus-induced ventricular tachycardia 18-24 h after permanent coronary occlusion were assessed. Experiments were performed on 32 mongrel dogs with temporary coronary occlusion lasting 20 min and subsequent reperfusion. Control ligations in 16 animals were compared to ligations after pretreatment with D (2 mg kg-1) in 6 dogs. In another 10 dogs a permanent coronary occlusion was performed and the inducibility of ventricular tachycardia was assessed by programmed stimulation before and after D (2.4 mg kg-1). Following D the incidence of ventricular arrhythmias including rapid ventricular tachycardias was not reduced during acute coronary occlusion, but even enhanced in some animals, whereas the frequency of ventricular fibrillation was diminished. No significant difference was observed following reperfusion. Conduction delay in the ischaemic area increased significantly during both phase Ia and Ib following pretreatment with D. During reperfusion conduction delay was significantly prolonged in the D group. At 18-24 h after permanent coronary occlusion the new compound proved to be highly effective in suppressing stimulus-induced ventricular tachycardia. During acute coronary occlusion D diminished the incidence of ventricular fibrillation. D is similar to other class Ic compounds; however, there are some important differences with respect to its additional beta-sympatholytic activity.

Efficacy of oral and intravenous indecainide in ventricular arrhythmias

To evaluate the efficacy of oral and intravenous indecainide, a new class IC antiarrhythmic agent, 3 separate protocols were performed in patients with benign or potentially lethal ventricular arrhythmias. An open-label intravenous trial in 10 patients was conducted using a dose of 1.7 mg/kg/min under constant monitoring. An oral short-term in-hospital trial in 20 patients (8 patients entered directly from the intravenous short-term trial) was conducted using a single-blind placebo dose titration protocol in which 50 mg of indecainide every 8 hours was increased at 3-day intervals to 75 mg, and then 100 mg every 8 hours depending on the observed change in ventricular arrhythmia frequency by Holter monitoring. Finally, an outpatient long-term oral trial was conducted in 17 of the 20 patients who completed the inpatient oral short-term trial. Two of the 10 patients from the inpatient intravenous trial did not enter the oral trial, because a proarrhythmic response developed in 1 and because of a lack of efficacy in the other. During the inpatient oral trial, 17 of 20 patients (85%) responded to indecainide and entered the long-term phase. Two of these patients were removed from the trial because of lack of efficacy at 3 and 10 months, respectively. In the oral therapy protocols, minor side effects of the central nervous system occurred in 4 of 17 patients (24%). Six of 20 patients (30%) each had more than a 25% increase in PR and QRS duration that was not associated with higher degrees of block. Thus, indecainide may be an effective and well tolerated class IC antiarrhythmic agent in patients with benign or potentially lethal ventricular arrhythmias.

Antiarrhythmic effects of indecainide in a drug-resistant population with ventricular tachycardia at programmed electrical stimulation

The antiarrhythmic properties of indecainide were studied in 15 patients with a history of a cardiac arrest or ventricular tachycardia. Programmed electrical stimulation studies were performed in nine men and six women with a mean age of 68 ± 2 years and a mean left ventricular ejection fraction of 41 ± 45. All patients had inducible ventricular tachycardia by programmed electrical stimulation while off all antiarrhythmic therapy. Patients were then tested on procainamide, 1000 mg, administered intravenously, and ventricular tachycardia could be provoked in 10 of 15 patients. Indecainide was given intravenously, 1 mg/kg. Indecalnide did not significantly change the baseline heart rate, blood pressure, and QT c interval from control values. The PR and QRS intervals were significantly prolonged. Twelve of 15 patients were still inducible for ventricular tachycardia on indecainide. Procainamide protected 5 of 15 patients against ventricular tachycardia induction. In patients still inducible on indecainide therapy, the ventricular tachycardia rate was significantly slowed, from 281 bpm to 224 bpm on indecainide and to 215 bpm on procainamide. The effects of this new class IC antiarrhythmic agent appears similar to procainamide in patients with sorious life-threatening tachyarrhythmias.

Effects of flecainide acetate on ventricular tachyarrhythmia and fibrillation in dogs with recent myocardial infarction.

The antiarrhythmic and antifibrillatory actions of the class IC antiarrhythmic agent flecainide acetate were examined in urethane-anesthetized dogs with recent myocardial infarction. The intravenous administration of flecainide in a loading dose of 1.0 mg/kg (n = 7) or 2.0 mg/kg (n = 6), followed by a maintenance infusion of 1.0 mg/kg/h to achieve plasma drug concentrations considered clinically therapeutic, failed to significantly elevate the electrical threshold current required to provoke ventricular fibrillation at infarct zone, border zone and non-infarct zone stimulation sites in postinfarction dogs. In 8 dogs which responded to baseline programmed stimulation with inducible sustained ventricular tachycardia, flecainide administered as 1.0 or 2.0 mg/kg loading doses followed by a 1.0 mg/kg/h maintenance infusion failed to prevent ventricular tachycardia initiation in any animal tested, although the post-treatment ventricular tachycardia cycle lengths were prolonged compared to baseline values (pre: 178 +/- 11 ms vs post: 202 +/- 17 ms, p less than 0.05). Flecainide administration apparently facilitated the induction of newly sustained ventricular tachycardia in 3 previously noninducible postinfarction dogs. The development of acute posterolateral ischemia at a site remote from previous anterior myocardial infarction resulted in the development of ventricular fibrillation in 4 of 11 (36%) saline-treated postinfarction dogs vs a cumulative 10 of 12 (83%) flecainide-treated, baseline noninducible postinfarction dogs (p less than 0.05 vs saline-treated). The incidence of sudden ischemic ventricular fibrillation was 7 of 7 (100%) among flecainide-treated baseline inducible postinfarction dogs. These data suggest that flecainide acetate may have only limited efficacy in preventing ventricular tachycardia or ventricular fibrillation soon after myocardial infarction.

Acute intravenous and long-term oral hemodynamic effects of encainide

The short- and long-term hemodynamic effects of encainide, a new class IC antiarrhythmic agent, were studied in 25 patients (mean age 61 ± 11) with complex symptomatic ventricular arrhythmia and left ventricular dysfunction. Ninety-two percent had previous myocardial infarction and 8% had dilated cardiomyopathy. Seventy-five percent had congestive heart failure, class III or IV, according to the New York Heart Association. All patients underwent a nuclear ventriculogram performed at least 3 days after discontinuing previous antiarrhythmic drugs. Nuclear ventriculograms were repeated 1 to 6 weeks later while the patients were receiving therapeutic doses of encainide ranging from 75 to 1,200 mg/day. Nuclear ventriculograms were also repeated after 6 months or 1 year of encainide therapy in 16 of these patients. Encainide did not have significant effects on heart rate, blood pressure, left ventricular ejection fraction, systolic or end-diastolic volumes. None of the patients showed a worsening of congestive heart failure during encainide therapy. These results compare favorably with those of other class I antiarrhythmic agents. A review of published reports on the hemodynamic effects of intravenous encainide shows it to have a mild but statistically significant dose-related depressant effect on cardiac function. This effect, however, appears to be no different from that of other newer class I agents.

Effects of encainide and its metabolites on energy requirements for defibrillation.

Encainide, a class IC antiarrhythmic agent, has been associated with proarrhythmic responses of ventricular tachycardia and fibrillation requiring defibrillation in patients. We examined the short-term effects of intravenous encainide and its two major metabolites, O-demethyl-encainide (ODE) and 3-methoxy-ODE (MODE), on the energy requirements for successful defibrillation in 25 pentobarbital-anesthetized, open-chest dogs. Truncated exponential (60% tilt) defibrillation shocks were administered through right atrial spring and left ventricular epicardial patch electrodes identical to those used in man with the automatic implantable defibrillator. At baseline multiple shocks of varying energy were applied to construct curves of percent successful defibrillation as a function of energy (DF curves) for each animal. Encainide, ODE, or MODE was then infused in loading and maintenance doses to achieve QRS widening of 20% to 50%. Saline was administered to animals serving as controls. Determination of the DF curve was repeated, after which the infusion was discontinued. After 1 hr washout period, an additional DF curve was constructed. The data were analyzed by logistic regression, and the energies required for 50% successful defibrillation (E50) were compared. No significant differences existed between the four groups in body or heart weight, extent of QRS widening, or baseline E50 values. After administration of encainide and ODE, the E50 increased by 129 +/- 43% (p less than .001) and 76 +/- 34% (p less than .005), respectively. Return of E50 toward baseline was observed after the washout periods in both groups (p less than .025), demonstrating the reversibility of the drugs' effects.(ABSTRACT TRUNCATED AT 250 WORDS)

The clinical electrophysiology of intravenous indecainide

The electrophysiologic effects of indecainide, a new class IC antiarrhythmic agent, were assessed in 10 patients with left ventricular dysfunction and inducible sustained ventricular tachycardia. Indecainide was administered intravenously in a dose of 60 to 90 mg/kg at a rate of 12.5 to 15 μg/kg/min. Indecainide had no effect on sinus node function or atrial and ventricular effective refractory periods. The AH (106 ± 13 vs 130 ± 24 msec, p <0.002) and HV (57 ± 7 vs 73 ± 19 msec, p <0.001) intervals were significantly increased. The QRS duration increased (102 ± 9 vs 120 ± 13 msec, p<0.001); however, the JT duration did not change. Induction of ventricular tachycardia was prevented in 1 of 10 patients. In the remaining nine patients, the ventricular tachycardia cycle length was significantly prolonged (248 ± 47 vs 320 ± 71 msec, p <0.001). Indecainide significantly depressed intracardiac conduction at several sites.

Aggravation of electrically provoked ventricular tachycardia during treatment with propafenone

Propafenone is a new class Ic antiarrhythmic agent currently being investigated in the United States. It is generally well tolerated. We administered propafenone to 16 patients with ventricular tachycardia (VT) that had been refractory to conventional antiarrhythmic drug therapy. Three of these 16 patients developed electrically provoked incessant VT during treatment with propafenone without other evidence of toxicity. These arrhythmias subsided after lidocaine was administered. Propafenone therapy was discontinued in each case. Incessant VT did not develop in any of these patients in the absence of antiarrhythmic drugs or on antiarrhythmic drugs other than propafenone. Alternative effective treatment was identified for each patient. Although VT was initially provoked by pacing in each of these patients, these observations suggest that propafenone, like some other class Ic drugs, may favor the development of incessant VT in occasional patients. This appears most likely to occur in patients with ventricular dysfunction and prior sustained VT or ventricular fibrillation.

Haemodynamic and antiarrhythmic effects of intravenous flecainide acetate in chronic congestive heart failure.

The objective of this study was to evaluate the haemodynamic and antiarrhythmic effects of flecainide acetate in patients with heart failure. Flecainide acetate, a class Ic antiarrhythmic agent, was given intravenously to 9 patients with congestive heart failure and frequent ventricular arrhythmias with nonsustained ventricular tachycardia. The drug (2 mg/kg) was infused slowly over 60 minutes. The maximum plasma level achieved was 218 (range 142-350) ng/ml. Six of the 9 patients experienced a 90% suppression of their arrhythmias for an average of 6.5 (range 2-15) hours. Pre-ejection period control (PEPc, 148.8 +/- 3.6 msec) increased to 157 msec and pre-ejection period/ejection time (PEP/ET) [control 0.449 +/- 0.027] to 0.516 (p less than 0.005), while the ejection time index (ETI) did not change. Cardiac index (control 2.4 +/- 0.36 L/min/m2) decreased by 11% (p less than 0.02), and pulmonary wedge pressure (control 13.4 +/- 2.4mm Hg) increased by 23% (p less than 0.05). Stroke work index, arterial pressure and vascular resistance did not change significantly. The parameters returned to control values on completion of the infusion. Flecainide acetate can be safely administered at the usual dose of 2 mg/kg to patients with congestive heart failure, provided that the infusion time is doubled. Antiarrhythmic efficacy under these conditions is good even at lower plasma concentrations.