Controversies in the treatment of hypercholesterolemia in the elderly: who should be treated and how?

High levels of low-density lipoprotein cholesterol may contribute to the development of coronary heart disease in the absence of other risk factors. This paper reviews major cholesterol prevention trials since 1994 concerning possible beneficial results of lowering cholesterol in persons over 65 years of age.

Genetic factors in human hypertension.

The advancement of molecular biomedical techniques has allowed solutions to the problem of finding a genetic linkage to hypertension. This is now being approached by limiting study to a select number of genetic factors possibly influencing a particular physiologic dysfunction or structural defect. Analysis of chromosomal abnormalities or regions bearing a particular mutation have been greatly influenced by the ability to produce artificial chromosomes or to identify closely linked markers. Rapid accumulation of knowledge of the genetic map has led to a number of these gene/disease linkages. Perhaps the unraveling of some of the polygenic influences in hypertension may lead to even better treatment protocols to minimize the disease complications of elevated blood pressure.

Effects of therapeutic concentrations of procainamide on transmembrane action potentials of normal and infarct zone Purkinje fibers and ventricular muscle cells.

Procainamide is a class I antiarrhythmic drug. Most studies of the cellular electrophysiologic effects of procainamide have been done with concentrations well above the therapeutic range. We studied the effects of therapeutic concentrations (10 mg/L) of the drug on transmembrane action potentials recorded from isolated canine cardiac tissues. In normal false tendon Purkinje fibers with maximal diastolic potentials (MDPs) of -93 +/- 1 mV, procainamide decreased action potential duration (APD)-20mV and slightly prolonged APD100%. The dV/dtmax was not decreased. In normal subendocardial Purkinje fibers with MDPs of -92 +/- 1 mV, procainamide 10 mg/L significantly decreased dV/dtmax but did not affect APD-20mV. In normal muscle cells from left ventricular endocardium, procainamide 10 mg/L increased only APD100%. The effects of procainamide on partially depolarized Purkinje fibers varied. In normal subendocardial Purkinje fiber preparations superfused with 7.5 mM KCl-Tyrode's solution, the mean maximal diastolic potentials were -73 +/- 2 mV, and procainamide 10 mg/L slightly decreased action potential amplitude (APA) and increased APD-60mV. In contrast, in 24-h infarct zone Purkinje fibers with MDPs of -75 +/- 4 mV, procainamide 10 mg/L decreased APA and dV/dtmax and prolonged APD100%. In one experiment on an infarct preparation, procainamide also induced 2:1 block at cycle lengths shorter than approximately 400 ms. The results of these experiments indicate that therapeutic concentrations of procainamide exert selective effects on action potentials in partially depolarized zones of infarcted hearts. This action may explain why procainamide can abolish some reentrant arrhythmias.

Local anesthetic and negative chronotropic effects of diltiazem on canine cardiac Purkinje fibers.

The electrophysiologic effects of diltiazem, a drug with antianginal, antihypertensive, and antiarrhythmic actions, were studied on transmembrane action potentials recorded from isolated canine cardiac tissues by means of standard microelectrode techniques. Recordings were made from normal canine cardiac Purkinje fibers in major false tendons, from normal Purkinje fibers partially depolarized by treatment with Tyrode's solution containing 7 mmol/L potassium chloride, from subendocardial Purkinje fibers of the left ventricle of normal hearts, and from subendocardial ventricular muscle preparations. Diltiazem, 1 and 2 mumol/L, exerted local anesthetic effects and decreased the action potential plateau duration in normal Purkinje fibers. In contrast, diltiazem, 1 mumol/L, did not affect the action potentials of potassium-depolarized Purkinje fibers, subendocardial Purkinje fibers, or ventricular muscle cells. Diltiazem, 1 and 2 mumol/L, did not decrease normal or high potential automaticity or catecholamine-enhanced high potential automaticity in canine Purkinje fibers with maximum diastolic potentials greater than -80 mV. In contrast, diltiazem, 1 mumol/L, rapidly terminated low potential automaticity in barium-treated Purkinje fibers with maximum diastolic potentials of -40 to -60 mV. The local anesthetic effects of diltiazem, as well as the effect on low potential automaticity, can explain the antiarrhythmic effects of the drug.

Does if control normal automatic rate in canine cardiac Purkinje fibers? Studies on the negative chronotropic effects of lidoflazine.

Lidoflazine has been reported to decrease the conductance of the slow inward current and of the pacemaker current (if) in cardiac tissues. We studied the effects of lidoflazine on normal and abnormal automaticity in isolated preparations of canine and ovine cardiac Purkinje fibers. Normal automaticity occurred in fibers with maximum diastolic potentials (MDPs) greater than -85 mV, and abnormal automaticity occurred in fibers with MDPs less than -60 mV. Normal automaticity was studied in fibers superfused with Tyrode's solution containing 2.7 mM KCl, 4 mM KCl, 4 mM KCl with 1 microM isoproterenol (ISO), and 4 mM KCl with 25 microM BaCl2. In each experiment, normal automatic rate was stable for at least 30 min before lidoflazine was added to the superfusate; lidoflazine did not decrease the rates significantly in any of the four series of experiments. However, when fibers with normal MDPs were pretreated with lidoflazine, the drug blunted the increase in rate that occurred 12-15 min after the start of exposure to ISO. However, lidoflazine significantly decreased abnormal automaticity induced by barium (250 microM or 5 mM). The results indicate that normal automaticity in Purkinje fibers is not affected by lidoflazine and is probably not controlled by if. Rather, normal rate is controlled by the magnitude of background potassium conductance (gK), as indicated by the significant effects of barium (25 microM) on rate. Lidoflazine may blunt the effects of ISO on rate by inhibiting if, but after ISO rhythms are established, they are probably maintained by triggered impulses that are not affected by lidoflazine. Lidoflazine may slow abnormal automaticity by inhibition of the slow inward current.

Comparative efficacy of pirmenol and procainamide in a drug-resistant population with ventricular tachycardia.

The acute antiarrhythmic properties of pirmenol were studied in 12 patients who failed clinical oral drug therapy with a history of a cardiac arrest or sustained ventricular tachycardia (VT). Programmed electrical stimulation studies were performed in ten men and two women with a mean age of 63 +/- 2 years. All patients had inducible ventricular tachycardia by programmed electrical stimulation when they were off all antiarrhythmic therapy. Patients were then tested on procainamide, 1000 mg, administered intravenously, and ventricular tachycardia could be provoked in nine of twelve patients. Pirmenol was given intravenously, 1.1 mg/kg bolus followed by 40 micrograms/kg/min over 40 minutes prior to drug testing. Pirmenol did not significantly change the baseline heart rate, blood pressure, or measured electrocardiographic values from control values. Ten of 12 patients were still inducible to ventricular tachycardia on pirmenol. Procainamide protected one of nine patients against VT induction. In patients still inducible on drug therapy, the VT rate was significantly slowed from 221 beats/min to 166 beats/min on pirmenol and to 200 beats/min on procainamide. The effects of this new antiarrhythmic agent were similar to procainamide in this drug-resistant study population.

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 +/- 4%. 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. Indecainide did not significantly change the baseline heart rate, blood pressure, and QTc 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 serious life-threatening tachyarrhythmias.

Antiarrhythmic efficacy of ethmozine in patients with ventricular tachycardia as determined by programmed electrical stimulation.

The antiarrhythmic properties of ethmozine were studied in 27 patients with a history of a cardiac arrest or symptomatic ventricular tachycardia. Programmed electrical stimulation studies were performed in 20 men and seven women with a mean age of 62 years and a mean left ventricular ejection fraction of 43%. All patients had inducible ventricular tachycardia by programmed electrical stimulation while off all antiarrhythmic therapy. Patients were then tested on procainamide if their treatment with this drug orally had not previously failed. Procainamide, 1000 and 1500 mg, was administered intravenously, and ventricular tachycardia could be provoked in 14 of 18 patients. Ethmozine was given in an oral loading regimen starting 24 to 36 hours later. After 500 mg oral ethmozine, patients were given 15 mg/kg ethmozine every 8 hours for seven to nine doses prior to drug testing. Ethmozine did not significantly change the baseline heart rate, blood pressure, and QTc interval from the initial drug-free values. The PR and QRS intervals were significantly prolonged. Seven patients were protected on oral ethmozine; 14 patients still had ventricular tachycardia inducible at programmed electrical stimulation testing, and six patients developed ventricular tachycardia spontaneously on ethmozine and were not tested in the programmed electrical stimulation laboratory. One patient had gastrointestinal complaints and was not discharged on the drug. The five patients who tolerated the oral protocol without side effects and who were protected against programmed stimulation induction of ventricular tachycardia were discharged on oral therapy. One patient on long-term therapy appeared to develop an allergic reaction to the agent with unexplained fevers and was switched to amiodarone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Lorcainide therapy in a cardiac arrest population.

Thirty-eight patients with prior history of cardiac arrest underwent programmed electrical stimulation (PES) studies and serial drug testing. Lorcainide was tested acutely in all 38 patients and prevented ventricular tachycardia (VT) or ventricular fibrillation (VF) induction in 14 patients and failed in 24 (efficacy rate 37%). Procainamide had failed clinically (cardiac arrest or breakthrough VT) in 16 patients, seven patients had previously severe adverse side effects, and thus only 15 were tested on procainamide at PES testing with seven protected. Following initial studies, 14 patients were started on lorcainide oral therapy and 24 on other therapy determined effective at PES testing (N-acetylprocainamide-two, flecainide-nine, bethanidine-three, slow-release procainamide hydrochloride-three, quinidine-two, cibenzoline-one, amiodarone-four). After 29 +/- 7 months follow-up, three are alive on lorcainide therapy, five discontinued therapy due to side effects; six died--three sudden deaths (33%) and two cardiac deaths (both myocardial infarctions). Twenty out of 24 patients are alive who were started on PES predicted effective therapy other than lorcainide; four died--three sudden deaths (13%) and one cardiac nonsudden death. Antiarrhythmic therapy guided by PES studies gives overall encouraging results in a cardiac arrest group of patients. Lorcainide, however, is not tolerated well and affords less protection against a sudden death recurrence than is noted in a population on other antiarrhythmic therapy predicted effective at PES testing.

QT prolongation and the antiarrhythmic efficacy of amiodarone.

Amiodarone is an antiarrhythmic agent known to cause prolongation of action potential duration which is reflected in the electrocardiogram as a prolongation of the QT interval. Prolongation of the QT interval in patients dying suddenly was compared with that in patients who remained alive to determine whether a difference existed between these two groups. The electrocardiogram and amiodarone levels were evaluated in 33 patients who presented with cardiac arrest and symptomatic ventricular tachycardia in whom no other antiarrhythmic agent was found effective in preventing induction of ventricular tachycardia during electrophysiologic studies. There were 30 men and 3 women (mean age 52 +/- 10 years). Twenty-three are alive after a mean follow-up period of 12 +/- 7 months. Ten died: six suddenly, three of non-cardiac causes and one of congestive heart failure. Using a two-way analysis of variance, the percent change in QT, QTc, JT and JTc intervals before and after amiodarone therapy was analyzed. Marked prolongation in the QT interval was present in patients who remained alive with amiodarone therapy. A significant difference in percent QT prolongation was seen between the latter patients and those who died suddenly (p less than 0.005). No difference was observed in the percent change in QRS interval between the two groups. The levels of amiodarone (2.5 versus 3.2 micrograms/ml) and its metabolite (desethylamiodarone) were not significantly different between the living patients and those who died suddenly. These findings suggest that a prolongation of the QT interval may be a marker for the therapeutic antiarrhythmic effect of amiodarone.

Electrophysiologic evaluation of the antiarrhythmic effects of N-acetylprocainamide for ventricular tachycardia secondary to coronary artery disease.

Antiarrhythmic properties of N-acetylprocainamide (NAPA), an active metabolite of procainamide, were studied in 12 patients with coronary artery disease who presented with cardiac arrest or documented sustained ventricular tachycardia (VT). Programmed electrical stimulation (PES) studies were performed in 10 men and 2 women, aged 52 to 80 years (mean 63), who had a left ventricular ejection fraction of 16 to 69% (mean 33). All patients tested had inducible VT provoked by PES without antiarrhythmic therapy. Patients were then tested with procainamide, 1,000 mg administered intravenously. VT could be provoked after procainamide treatment in 8 of 10 patients. Twenty-four to 36 hours later NAPA was administered, 18 mg/kg body weight intravenously, and PES was performed after 20 minutes. NAPA did not significantly change heart rate, mean arterial blood pressure, electrocardiographic intervals and AH or HV conduction times. The QT interval lengthened, but not significantly. The mean serum NAPA levels were 15.7 +/- 4 micrograms/ml in the group protected by NAPA and 16.2 +/- 4 micrograms/ml in the group not protected by NAPA. Five patients were discharged with NAPA therapy, 1.5 g orally every 8 hours. Two patients have been maintained with chronic NAPA therapy (10 +/- 3 months), and 2 patients had breakthrough VT on follow-up Holter monitoring and alternative therapy was given. One patient died while taking oral therapy. NAPA demonstrates antiarrhythmic efficacy in preventing induction of VT by PES in a high-risk group of patients. During chronic oral therapy in some patients, NAPA appears to be well tolerated, with antiarrhythmic efficacy that may be enhanced with further upward dose titration.

Cellular mechanisms of digitalis action.

Although the therapeutic actions of digitalis glycosides have been known for over 200 years, their direct inotropic actions on the heart were not established until the last 50 years. Digitalis has undergone intense research, particularly with respect to its mechanisms of action. Many authors have claimed to have found the true mechanism of action, compounding the complexity of literature. Recent subcellular studies have pointed to specific areas of action of the digitalis glycosides. Each discovery has been dependent on the greater understanding of the electrophysiologic characteristics of cardiac muscle and excitation-contraction coupling. The current hypothesis suggests that digitalis specifically inhibits Na-K ATPase. This produces an elevation in intracellular sodium level that in turn produces an increase in the intracellular calcium level. The increased quantities of calcium available to the contractile elements of cardiac muscle provide the observed increased inotropy.

Antiarrhythmic effects of cibenzoline.

Thirty-three patients with ventricular tachyarrhythmias were referred for evaluation of their arrhythmias using programmed electrical stimulation to guide antiarrhythmic therapy. Cibenzoline succinate, a new antiarrhythmic agent, was compared to procainamide in patients with ventricular tachycardia. Cibenzoline was given intravenously, initially 1.0 mg/kg, then in 1 mg/kg increments to a maximum of 3.0 mg/kg, during electrophysiologic testing. The results were compared to procainamide, which was also administered intravenously to 1000 and then to 1500 mg. Cibenzoline provided protection against ventricular tachycardia induction in 16 of 33 patients. The PR interval increased 13%, QRS duration widened 26%, and QTc interval was prolonged by 7%. There was a 9% fall in mean arterial blood pressure. Procainamide prevented ventricular tachycardia induction in 21 out of 31 patients tested. The PR interval increased 11%, QRS duration widened 27%, and QTc interval prolonged by 8%. Cibenzoline was given orally to 13 patients for chronic treatment. Chronic oral cibenzoline therapy after a mean follow-up of 8.8 months caused a reduction of ventricular ectopy from 666 to 190 beats/hr. Ventricular tachycardia events decreased per Holter monitor recording from 6 to 0.6. Cibenzoline therapy was discontinued in 5 of 13 patients due to break-through arrhythmias (nonsustained ventricular tachycardia on Holter monitor and recurrence of symptoms). Cibenzoline may be an effective antiarrhythmic agent in selected patients.

Therapy for late post infarction ventricular tachycardia.

Non-sustained ventricular tachycardia (VT) in the late post myocardial infarction (MI) period (7-21 days) has been reported to be a predictor of sudden death. We suspected that patients with 3 beat VT on Holter monitoring in the late infarction period would demonstrate electrical instability at electrophysiologic studies. Forty-seven patients were identified as having at least 3 beat VT on Holter monitoring. Eighteen patients refused electrophysiologic studies or were not referred by their attending physician. The mean ejection fraction of this group was 43 +/- 16%. Eight patients have died, 3 sudden deaths in 13 +/- 5 months, a 17% incidence of sudden death. Twenty-nine patients underwent invasive electrophysiologic studies. Their mean ejection fraction was 37 +/- 7%, and 28 had inducible, 18 sustained ventricular tachycardia and 10 non-sustained VT. No complications were noted with electrophysiological testing in the post infarction patients. Using programmed electrical stimulation studies an effective antiarrhythmic agent preventing VT induction (usually experimental) could be found for each patient. After a mean follow-up of 12.5 +/- 4 months, the patient without inducible VT is alive and 26 of the 28 "inducible" patients are alive and well. Two patients died, one of stroke and one due to pump failure following a second MI. No sudden deaths were observed in this group. Two patients had breakthrough arrhythmias and were treated by alternative antiarrhythmic therapy that was also effective at the initial electrophysiologic studies. Thus, PES studies post MI are safe and may be an effective way to assess therapy for patients in the early post MI period, identified at high risk for sudden death.

Electrophysiological effects of bethanidine sulfate on canine cardiac Purkinje fibers and ventricular muscle cells.

Bethanidine sulfate is a congener of bretylium tosylate, which has been reported to have antiarrhythmic and antifibrillatory effects. We studied the effects of bethanidine on transmembrane potentials recorded from canine Purkinje fibers and ventricular muscle cells, using standard microelectrode techniques. Normal Purkinje fibers were exposed to bethanidine (10-80 mg/L) for 30-40 min. Bethanidine produced dose-dependent decreases in the maximal rate of depolarization (MRD) and over-shoot of phase 0, but did not affect maximum diastolic potential (MDP). Action potential plateau duration (APD, to -60 mV) was decreased by bethanidine at all cycle lengths of stimulation between 1,000 and 300 ms. Bethanidine depressed the membrane responsiveness curve, and its effects on MRD showed marked use dependence. In ventricular muscle cells, bethanidine 20 mg/L decreased MRD but did not affect MDP or APD. The rate of normal automaticity in Purkinje fibers with MDPs greater than -85 mV was increased to 21.5 +/- 5.6 beats/min after exposure to bethanidine (10 mg/L for 30 min) from control values of 10.2 +/- 5.3 beats/min. Abnormal automaticity (MDPs = -40 to -60 mV) was induced in Purkinje fibers by superfusion with Tyrode solution containing 0.25 mM BaCl2; this activity also was accelerated after exposure to bethanidine 10 mg/L. The effects of bethanidine on automaticity are similar to those of bretylium, and may be caused by release of endogenous catecholamines. In contrast, the effects of bethanidine on action potentials of normal (driven) Purkinje fibers are markedly different from those of bretylium, and resemble those of lidocaine after 30-60 min of exposure.

Antiarrhythmic action of bethanidine.

Studies were performed in 20 patients with symptomatic ventricular tachycardia (VT) to determine the efficacy of bethanidine compared with procainamide in preventing VT induced by programmed electrical stimulation. Before administering bethanidine, 5 to 10 mg/kg, the patients received 15 mg of protriptyline orally 24 and 2 hours before electrophysiologic studies to prevent the orthostatic hypotensive effects of bethanidine. Sustained VT (VT not spontaneously stopping) was induced in 8 and nonsustained VT (10 beats or more, terminating spontaneously) was induced in 4 patients. Bethanidine, 5 mg/kg, protected in 7 patients, and 10 mg/kg protected 1 additional patient. Procainamide, 1,000 and 1,500 mg intravenously, protected 8 of 16 patients. Bethanidine prevented VT induction in 50% of the patients not protected by procainamide. Bethanidine facilitated VT induction in 3 patients, while procainamide facilitated VT induction in 1 patient. Four patients with symptomatic VT have received bethanidine therapy for an average of 11 +/- 1.3 months, without clinical recurrence of their VT. Concomitant administration of protriptyline attenuated the acute hemodynamic changes caused by bethanidine and chronic combined therapy of protriptyline and bethanidine abolished the severe orthostatic changes in blood pressure caused by bethanidine. These studies show that bethanidine is effective in preventing VT induction and, thus, its use may not be restricted only to cases of primary ventricular fibrillation.

Lorcainide therapy for the high-risk patient post myocardial infarction.

Nonsustained ventricular tachycardia (VT) in the late period (7 to 21 days) after myocardial infarction (MI) is reported to be a predictor of sudden death. Patients with 3-beat VT on Holter monitoring in the late infarction period would be suspected to demonstrate electrical instability on electrophysiologic studies. Forty-seven patients were identified as having at least 3-beat VT on Holter monitoring. Eighteen patients refused electrophysiologic studies or were not referred. Eight patients died; 3 were sudden deaths in 13 +/- 5 months, a 17% incidence. Twenty-nine patients underwent invasive electrophysiologic studies and 28 had inducible VT, 18 sustained and 10 nonsustained. Lorcainide prevented VT induction in 21 of the 28 patients, whereas 12 of the 22 patients studied on procainamide were protected. Lidocaine, tested in 21 patients, prevented VT induction in only 5. Lorcainide and procainamide prolonged refractoriness in those patients protected at programmed electrical stimulation (PES), whereas the QT interval was prolonged in patients in whom VT could still be induced. Twenty-seven of the 28 patients were placed on drugs predicted to be effective by PES studies, 19 on lorcainide. After a mean follow-up of 12.5 +/- 4 months the patient with noninducible arrhythmia is alive and 26 of the 28 patients with inducible arrhythmia are alive and well. Two patients died, 1 of stroke and 1 of pump failure after a second MI. No sudden deaths were observed in this group. Two patients had breakthrough arrhythmias and were treated by alternative antiarrhythmic therapy that was also effective on initial electrophysiologic studies.(ABSTRACT TRUNCATED AT 250 WORDS)

New directions in the development of antiarrhythmic drugs.

To identify new antiarrhythmic drugs and their mechanisms of actions, it has been necessary to use appropriate models to describe arrhythmias. Recently introduced concepts in cellular electrophysiology of arrhythmias provide the newest models in which drug development have been attempted. Arrhythmias have been attributed to abnormalities of conduction, abnormalities of impulse formation, or a combination of both. Recent descriptions of abnormally triggered rhythms have been ascribed to a phenomenon called after depolarizations. An ionic basis for the formation of these arrhythmias has been recently described. Further, specificity of the drug effects at a cellular level to modify these arrhythmias are being observed by a variety of new techniques. Microelectrode methods have provided direct access to the intracellular milieu to determine the biophysical changes brought about by antiarrhythmic agents. These observations have led to a greater understanding of the underlying abnormalities at the cellular level. Testing of antiarrhythmic drugs in the intact heart has led to the development of clinical use of invasive electrophysiologic techniques. Intracardiac catheters are being used to describe abnormalities of impulse initiation as well as conduction. Efficacy of antiarrhythmic drugs in the intact heart may be determined with greater accuracy using these techniques. Abnormal rhythms can be initiated and terminated using intracardiac catheter methods with antiarrhythmic agents as therapeutic adjuncts.

Pacing termination of ventricular tachycardia: influence of antiarrhythmic-slowed ectopic rate.

The success of pacing stimuli interruption of ventricular tachycardia (VT) was examined in 77 episodes of sustained VT induced in 31 patients undergoing programmed electrical stimulation studies. Once VT was induced, a trial to terminate the arrhythmia by means of the technique of entrainment was attempted. If this failed, rapid burst pacing faster than the VT was begun to try and terminate the tachycardia. In 30 patients off antiarrhythmic agents, entrainment was effective in terminating VT in 27%, while burst pacing was also effective in 27%. In 37% of patients, VT was accelerated or ventricular fibrillation was produced by pacing techniques, and these patients required defibrillation. Following antiarrhythmic therapy that failed to prevent VT induction but did result in slowing of VT rate, entrainment was only successful in 23% of trials, while burst pacing was successful in 34% of trials. The incidence of acceleration of VT on therapy was 32%. There was no appreciable difference in acceleration noted with or without antiarrhythmic therapy. Regardless of therapy, the slower the VT rate, the greater success of pacing termination of VT and the lower the incidence of VT acceleration. Antiarrhythmic agents that significantly slow the VT rate increase the success rate of pacing stimuli interruption of VT and decrease the incidence of VT acceleration and thus the need for defibrillation. The results suggest that antiarrhythmic agents that slow the VT rate may increase the effectiveness of antiarrhythmic pacemakers in terminating VT.