Relation of interleukin-6 and C-reactive protein levels to sinus maintenance after pharmacological cardioversion in persistent atrial fibrillation.

OBJECT: The aim of this study was to investigate whether interleukin-6 (IL-6) and C-reactive protein (CRP) have significant relation to sinus maintenance after pharmacological conversion of long-lasting atrial fibrillation (AF) with respect to use of renin-angiotensin-aldosterone system (RAS) inhibitors. METHODS: We studied 35 consecutive patients with AF lasting > or =1 month who had successful pharmacological cardioversion with bepridil alone or in combination with aprindine. The IL-6 and CRP levels in plasma were measured after pharmacological restoration of sinus rhythm. RESULTS: During the 1-year follow-up period, sinus rhythm was maintained in 20 patients (Group I), and the other 15 patients had recurrence of AF (Group II). Both plasma levels of IL-6 and CRP were significantly lower in Group I than in Group II (IL-6: 1.19 +/- 0.51 versus 1.84 +/- 0.66 ng/L, P < 0.005; CRP: 0.59 +/- 0.40 versus 1.24 +/- 0.79 mg/L, P < 0.005). The use of RAS inhibitors and left atrial dimension and the left ventricular ejection fraction showed no differences between the 2 groups. There was significant positive correlation between levels of IL-6 and CRP. CONCLUSION: In long-lasting persistent AF, lower levels of IL-6 and CRP appear to be associated with maintenance of sinus rhythm after pharmacological cardioversion irrespective of the use of RAS inhibitors. Further studies are needed to clarify the role of RAS inhibitors.

[Strategy for cardiac arrhythmias in acute coronary syndrome].

Acute coronary syndrome causes several types of arrhythmia because of its electrical instability and ischemia. The most important arrhythmia is ventricular tachycardia which degenerates to ventricular fibrillation. Prompt direct current cardioversion will be needed and prevention of ventricular tachyarrhythmia by potassium channel blocker became more popular in Japan. Nifekalant or amiodarone should be selected. Atrial fibrillation also occurred in the patients with acute coronary syndrome, and it may deteriorate hemodynamics condition. Therefore, termination and prevention of atrial fibrillation is another important issue in acute coronary syndrome. Aprindine, amiodarone, or bepridil will be the choice to prevent recurrent atrial fibrillation after direct current cardioversion.

Nonlinear mixed effects model analysis of the pharmacokinetics of routinely administered bepridil in Japanese patients with arrhythmias.

This study was performed to evaluate variability in the pharmacokinetics of bepridil in 38 Japanese patients with arrhythmias, and to investigate the effects of aprindine as well as CYP2D6 and CYP3A5 polymorphisms on the oral clearance of bepridil. We determined the polymorphic alleles of CYP2D6 and CYP3A5 in each subject. The plasma concentration of bepridil at steady-state following repetitive oral administration was measured with an HPLC-based method, and the oral clearance was estimated using the nonlinear mixed effects model (NONMEM) program. Mean oral clearance was significantly greater in the patients with the CYP2D6*10 allele than in those without it. On the other hand, no significant effect of the CYP3A5 polymorphism was observed on the pharmacokinetics of bepridil. In addition, aprindine seemed to reduce the oral clearance of bepridil in the patients with the CYP2D6*10 allele.

Drug-induced changes in fibrillation cycle length and organization index can predict chemical cardioversion of long-lasting atrial fibrillation with bepridil alone or in combination with aprindine.

BACKGROUND: The aim of this study was to investigate whether drug-induced changes in fibrillation wave characteristics can predict pharmacological conversion of long lasting persistent atrial fibrillation (AF). METHODS AND RESULTS: The study group comprised 23 consecutive patients with AF lasting > or =1 month. Patients first received bepridil (200 mg/day) for 2-4 weeks. When sinus rhythm was not restored with bepridil, oral aprindine (40 or 60 mg/day) was added to bepridil. Fast Fourier transform analysis of fibrillation waves using lead V1 was performed to calculate the fibrillation cycle length (FCL). The spectral areas were measured and the maximum area divided by the total area was termed the fibrillation organization index (FOI). Sinus rhythm was restored in 16 of 23 patients (70%); 8 of these 16 patients received only bepridil (Group I) and the other 8 responders received bepridil and aprindine (Group II). In Group I bepridil increased both FCL (p<0.001) and FOI (p<0.01) and terminated AF after 20+/-12 days. In Group II bepridil increased FCL (p<0.001), but did not change FOI. The addition of aprindine terminated AF in association with an increase in both FCL (p<0.005) and FOI (p<0.005) within 19+/-8 days. In the remaining 7 patients who did not have restoration of sinus rhythm, bepridil increased both FCL and FOI significantly, but less than in Group I, and the addition of aprindine did not further increase either of them. Chemical cardioversion of AF occurred in all patients with FCL > or =190 ms and FOI > or =45% after drug administration. CONCLUSION: Bepridil alone or in combination with aprindine converted long lasting persistent AF in association with an increase in both FCL and FOI. The combination of FCL and FOI after drug administration is helpful in predicting chemical cardioversion of persistent AF.

Maintenance of sinus rhythm and recovery of atrial mechanical function after cardioversion with bepridil or in combination with aprindine in long-lasting persistent atrial fibrillation.

BACKGROUND: The aim of this study was to evaluate pharmacological cardioversion of long-lasting persistent atrial fibrillation (AF) using bepridil in terms of recovery of atrial mechanical function and maintenance of sinus rhythm. Bepridil alone or in combination with aprindine is effective for termination of persistent AF. METHODS AND RESULTS: The study group comprised 38 consecutive patients (24 men, 58.8+/-9.3 years) with successful conversion of persistent AF lasting >1 month either pharmacologically (Group I) or electrically (Group II). Fast Fourier transform analysis of fibrillation waves was performed and fibrillation cycle length (FCL) was calculated from the peak frequency. In Group I, sinus rhythm was pharmacologically restored in 22 patients after an average 30 days (7-49 days) of bepridil administration, either alone (11) or in combination with oral aprindine (11); they were followed up while using the same drugs. In Group II, electrical conversion restored sinus rhythm in 16 patients, and they were followed up with conventional antiarrhythmic drugs other than bepridil and aprindine. After bepridil treatment FCL increased and became significantly longer in Group I than in Group II (190+/-39 vs 150+/-29 ms, p<0.001). Atrial peak velocity in transmitral flow within the first week after cardioversion was greater in Group I than in Group II (68+/-35 vs 32+/-20 cm/s, p<0.05). By Kaplan-Meier analysis, 83% of Group I patients were free of AF recurrence at the 12-month follow-up, compared with 36% in Group II (p<0.005). CONCLUSIONS: In patients with long-lasting AF, pharmacological conversion with bepridil alone or in combination with aprindine recovered atrial mechanical function better and maintained sinus rhythm longer than electrical conversion.

Usefulness and safety of bepridil in converting persistent atrial fibrillation to sinus rhythm.

The aim of this study was to investigate the efficacy and safety of bepridil (a multichannel blocker including several potassium channels) for conversion of long-lasting atrial fibrillation (AF). Bepridil restored sinus rhythm alone or in combination with aprindine in 69% of 32 patients with persistent AF lasting > or = 3 months. The time to conversion after starting bepridil was 30 +/- 12 days. An increase in fibrillation cycle length with bepridil was greater in responders (31 +/- 10%), but an increase in QTc did not differ between responders and nonresponders. Bepridil is effective and safe for terminating long-lasting persistent AF.

[Comparison of the efficacies of disopyramide, cibenzoline and aprindine for the termination of paroxysmal and persistent atrial fibrillation in elderly and non-elderly patients].

OBJECTIVES: The relationship between the efficacy of the anticholinergic action of disopyramide, cibenzoline and aprindine and age was examined in patients with paroxysmal and persistent atrial fibrillation. METHODS: This prospective, randomized study included 278 patients (200 men, 78 women, mean age 61 +/- 11 years) divided into two groups; the non-elderly group (age below 60 years) and the elderly group (age over 60 years). Successful termination was defined as conversion of sinus rhythm within 30 min of intravenous administration of 50 mg disopyramide (n = 91), 70 mg cibenzoline (n = 93) or 100 mg aprindine (n = 94) in this prospective and randomized study. RESULTS: No statistically significant difference was found in patient characteristics between the three agents. 1) The rate of conversion to sinus rhythm after disopyramide administration in the non-elderly group(37.8%) was significantly higher than that in the elderly group (17.4%, p = 0.0361). 2) The rate of conversion to sinus rhythm after cibenzoline administration in the non-elderly group (62.2%) tended to be greater than that in the elderly group (43.8%, p = 0.0972). 3) The rate of conversion to sinus rhythm after aprindine administration in the non-elderly group (25.6%) was not significantly higher than that in the elderly group (18.2%, p = 0.4474). CONCLUSIONS: The anticholinergic action of antiarrhythmic agents has an effect on successful termination in non-elderly patients with paroxysmal and persistent atrial fibrillation.

Atrial fibrillation threshold predicted long-term efficacy of pharmacological treatment of patients without structural heart disease.

AIMS: To ascertain if an electrophysiological study could predict long-term efficacy of anti-arrhythmic drugs in the treatment of lone atrial fibrillation. METHODS AND RESULTS: Forty-four patients (36 males, 8 females, age 55.5 +/- 10.6) with paroxysmal atrial fibrillation were enrolled to undergo serial electrophysiological studies at the bedside. Two quadripolar catheters were inserted via the subclavian vein. Disopyramide (D: 2 mg/kg iv), cibenzoline (C: 1.4 mg/kg iv), aprindine (A: 2 mg/kg iv), pilsicainide (P: 2 mg/kg po) and flecainide (F: 3 mg/kg po) were tested. Atrial fibrillation threshold (AFT) was measured as the lowest current amplitude of rapid pacing (50 Hz for 1 s) to induce atrial fibrillation lasting more than 30 s. Before drug treatment, AFT was 3.9 +/- 0.3 mA. Pharmacological treatment raised AFT as follows: D 5.9 +/- 0.9 mA, C 7.6 +/- 1.2 mA, A 8.1 +/-1.1 mA, P 6.0 +/- 0.8 mA, F 7.3 +/- 1.1 mA. Recurrence of atrial fibrillation was observed during 1-year follow-up in 12% of cases when they were treated with a drug that raised AFT by 5 mA or more. On the other hand, the recurrence rate was 87% when patients were treated with a drug that raised AFT by less than 5 mA (P = 0.001). CONCLUSION: AFT was a good predictor of long-term efficacy of pharmacological treatment against atrial fibrillation.

Double-blind placebo-controlled trial of aprindine and digoxin for the prevention of symptomatic atrial fibrillation.

A multicenter, placebo-controlled, randomized, double-blind trial compared the preventive effect of aprindine and digoxin on the recurrence of atrial fibrillation (AF) with placebo, and also compare the effectiveness of these 2 drugs in the prevention of AF. Patients with symptomatic paroxysmal or persistent AF who had converted to sinus rhythm (SR) were randomly assigned aprindine (40 mg/day), digoxin (0.25 mg/day) or placebo and followed up on an outpatient basis every 2 weeks for 6 months. Of the 141 patients from 36 participating centers, 47 were given aprindine, 47 digoxin, and 47 were on placebo. After the 6-month follow-up, the Kaplan-Meier estimates of the percentage of patients remaining free of recurrent symptomatic AF on aprindine, digoxin and placebo were 33.3%, 29.2% and 21.5%, respectively. In patients remaining in SR for 15 days after from the start of follow-up, freedom from recurrence was significantly more prevalent in the aprindine group than in the placebo group (p=0.0414), but there was no significant difference between the digoxin and placebo groups. The rate of adverse events was similar in the 3 groups. In conclusion, neither aprindine nor digoxin had a significant effect on preventing relapse of symptomatic AF; however, recurrence of AF occurred later with aprindine than with placebo or digoxin.

Inhibitory effect of aprindine on Na+/Ca2+ exchange current in guinea-pig cardiac ventricular myocytes.

1. Using the whole-cell voltage clamp technique, the effect of aprindine on Na+/Ca2+ exchange current (I(NCX)) was examined in guinea-pig single cardiac ventricular myocytes and CCL39 fibroblasts expressing a dog cardiac Na+/Ca2+ exchanger (NCX1). 2. I(NCX) was recorded by ramp pulses from the holding potential of -60 mV with the external solution containing 140 mM Na+ and 1 mM Ca2+, and the pipette solution containing 20 mM Na+, 20 mM BAPTA and 13 mM Ca2+ (433 nM free Ca2+). 3. External application of aprindine suppressed I(NCX) in a concentration-dependent manner. The IC50 values of outward (measured at 50 mV) and inward (measured at -100 mV) I(NCX) components were 48.8 and 51.8 microM with Hill coefficients of 1.3 and 1, respectively. 4. Intracellular application of trypsin via the pipette solution did not change the blocking effect of aprindine, suggesting that aprindine does not affect the exchanger from the cytoplasmic side. 5. Aprindine inhibited I(NCX) of a mutant NCX1 with a deletion of amino acids 247 - 671 in the large intracellular domain between the transmembrane segments 5 and 6 in a similar manner to that of the wild-type, suggesting that the site of aprindine inhibition is not in the large intracellular domain of NCX1. 6. A kinetic study indicated that aprindine was cooperatively competitive with KB-R7943, another inhibitor of NCX and that aprindine was a competitive inhibitor with respect to external Ca2+. 7. We conclude that aprindine may modestly inhibit I(NCX) in a therapeutic range of concentrations (around 2.5 approximately 6.9 microM) possibly at an external or intra-membranous site of the exchanger.

Effect of aprindine on heart rate variability indices in patients with ischemic heart disease.

BACKGROUND: Decreased heart rate variability indices (HRV) are associated with untoward outcome of patients with ischemic heart disease (IHD). Most class I antiarrhythmic agents decrease HRV, but aprindine (a new class I antiarrhythmic agent) is reported to increase HRV in patients without ischemia. HYPOTHESIS: The study was undertaken to determine whether apridine might increase HRV in patients with IHD. METHODS: To investigate the effect of aprindine on HRV in patients with IHD, we performed 24-h ambulatory electrocardiogram (ECG) at the end of placebo and aprindine (60 mg daily) treatment phases on 38 patients with IHD and at least isolated premature ventricular contractions (PVC). The study protocol utilized a single blind, 4-week, placebo-controlled design. Heart rate variability from ambulatory ECG included SDNN (ms), SDANN (ms), SD (ms), rMSSD (ms), pNN50 (%); frequency analysis of HRV consisting of total (ms, 0.01-1.00 Hz), low (ms, 0.04-0.15 Hz), and high (ms, 0.15-0.40 Hz) components. RESULTS: Study patients were divided into three groups according to the severity of IHD and antiarrhythmic efficacy of aprindine. Group 1 consisted of 15 patients with angina with single-vessel disease, and Group 2 was composed of 10 patients with either multivessel disease or post myocardial infarction; PVCs decreased in both groups as result of aprindine treatment. Group 3 consisted of 13 patients who showed no decreased PVC after aprindine treatment. RMSSD increased, and pNN50 and high-frequency spectra tended to increase in Group 1, while SD, rMSSD, pNN50, and total and low-frequency spectra decreased in Group 3; no significant changes were observed in Group 2. Aprindine significantly augments vagal activity, as reflected by the increase of rMSSD, pNN50, and high-frequency spectra in mild IHD. CONCLUSION: These salutary effects are less in more severe IHD, but aprindine does not aggravate HRV. Thus, if there are salutary effects on arrhythmias and no proarrhythmic effects, aprindine could be prescribed to patients with IHD without concern about decreasing HRV.

Effects of aprindine on ischemia/reperfusion-induced cardiac contractile dysfunction of perfused rat heart.

The present study was undertaken to determine whether aprindine, a class Ib antiarrythymic agent, exerts beneficial effects on ischemia/reperfusion-induced cardiac contractile dysfunction and metabolic derangement. Isolated rat hearts were subjected to 35-min global ischemia, followed by 60-min reperfusion, and functional and metabolic alterations of the heart were determined with or without aprindine-treatment. Ischemia induced a cessation of left ventricular developed pressure (LVDP), a rise in left ventricular end-diastolic pressure (LVEDP), and an increase in myocardial sodium content and a decrease in myocardial potassium content. When the hearts were reperfused, little recovery of LVDP and sustained rise in LVEDP and perfusion pressure were observed. Ischemia/reperfusion resulted in a release of ATP metabolites and creatine kinase from perfused hearts, an increase in myocardial sodium and calcium contents, and a decrease in myocardial potassium and magnesium contents. Treatment of the perfused heart with either 10 or 30 microM aprindine for the last 3 min of pre-ischemia improved contractile recovery during reperfusion and suppressed changes in myocardial ion content during ischemia and reperfusion. Treatment with the agent also attenuated the release of ATP metabolites and creatine kinase from the heart. However, treatment with high concentrations of aprindine (70 and 100 microM) improved neither cardiac contractile dysfunction, myocardial ionic disturbance nor the release of ATP metabolites and creatine kinase during reperfusion. Two possible mechanisms for the cardioprotection by the agent have been suggested: suppression of transmembrane flux of substrates and enzymes, and prevention of accumulation of myocardial sodium during ischemia.

Complex frequency-dependent interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction.

We investigated the interaction of class-I antiarrhythmic drugs as they affect intraventricular conduction of human hearts in vivo. QRS duration in signal-averaged electrocardiograms and standard electrocardiograms were measured as an index of intraventricular conduction time in 17 patients with implanted pacemakers at various pacing rates (100-180 ppm, VVI mode). Single intravenous administration of lidocaine, disopyramide or aprindine prolonged the QRS of signal-averaged electrocardiograms in a frequency-dependent manner. Lidocaine (n = 17) produced significant QRS prolongation from pre-drug control at rates > or = 120 ppm (6.2 +/- 1.4% at 180 ppm), whereas disopyramide (n = 17) and aprindine (n = 17) did so from the lowest rate (8.9 +/- 1.8% to 12.3 +/- 2.9% at 100-180 ppm with disopyramide; 14.7 +/- 1.3% to 19.3 +/- 2.2% at 100-180 ppm with aprindine). Addition of lidocaine to disopyramide (n = 17) showed an additive effect; QRS prolongation was enhanced significantly by 1.4-2.8% at rates > or = 150 ppm. In contrast, addition of lidocaine to aprindine (n = 17) showed a subtractive effect; the QRS prolongation was attenuated significantly by 1.6-2.4% at rates < 150 ppm. Combined intravenous administration of class-I antiarrhythmic drugs causes not only additive but also subtractive effects on the intraventricular conduction of the human heart, probably through their interaction on the sodium channel receptor.

Effects of aprindine on electrophysiological properties of the atrial muscle in man.

The effects of aprindine on atrial vulnerability were studied in 11 patients; 9 with paroxysmal atrial fibrillation (PAF), and 2 with Wolff-Parkinson-White syndrome, aged 19 to 69 (55.9 +/- 16.5; mean +/- SD). Before and 10 min after the intravenous injection of aprindine (1.5 mg/kg), programmed extrastimulation was performed from the right atrial appendage. Atrial vulnerability was assessed by evaluating the repetitive atrial firing zone (RAFZ), conduction delay zone (CDZ), maximum conduction delay (Max. CD) and fragmented atrial activity zone (FAAZ). After the injection, the duration of the P wave and QTc interval was significantly prolonged without any change in blood pressure or heart rate. RAF was observed in 8 patients under control conditions. However, after the injection of aprindine, the RAFZ completely disappeared in 2 patients, was narrowed in 4, and became wider in 1. AF was induced in the remaining patient. The zone significantly reduced (p < 0.01) without any change in CDZ or Max. CD. While FAA was observed in 5 patients under control conditions, it completely disappeared in 2 patients, was narrowed in 1, and did not change in the remaining 7 after the injection of aprindine. In patients whose RAFZ narrowed after administration of aprindine, the wavelength, as determined from the atrial effective refractory period and conduction velocity, was augmented. These results indicate that aprindine suppresses atrial vulnerability with an augmentation of the wavelength. However aprindine exaggerated atrial vulnerability in some patients, such that atrial fibrillation was induced.

Aprindine-induced hepatic granulomata.

Aprindine is a very effective antiarrhythmic agent with a narrow therapeutic ratio. We report a patient who suffered from granulomatous hepatitis probably due to the administration of aprindine. Evidence of hepatitis appeared within 6 weeks of initiating aprindine therapy and resolved rapidly when the drug was withdrawn. Six months later, fibrosis but no granulomata were found in the expanded portal tracts. Our observations suggest that granulomatous hepatitis can occur during aprindine therapy.

Atrioventricular nodal reentrant tachycardia with retrograde block induced by aprindine.

Two patients are described who had atrioventricular nodal reentrant tachycardia (AVNRT) with 1:1 relationship in the control state, but in whom a varying degree of VA block during AVNRT was observed during therapy with aprindine. Aprindine, however, did not cause anterograde blockade of conduction over the slow AV nodal pathway during tachycardia. These observations support the conclusion that the bulk of atrial muscle is not a requisite part of the tachycardia circuit in AVNRT and that antiarrhythmic drugs may have disparate effects on conduction in the retrograde and anterograde limbs of the circuit.

Combination therapy with aprindine and verapamil for paroxysmal supraventricular tachycardia as assessed by transesophageal atrial pacing.

UNLABELLED: To assess the efficacy of combination therapy of aprindine (40 mg/day) and verapamil (160 mg/day), transesophageal programmed atrial stimulation was performed on 21 patients with paroxysmal supraventricular tachycardia (including 12 patients with atrioventricular nodal reentrant tachycardia and nine patients with atrioventricular reentrant tachycardia) under four conditions: a) control, b) aprindine alone, c) verapamil alone, and d) aprindine + verapamil. RESULTS: a) Aprindine, verapamil, and aprindine + verapamil prevented paroxysmal supraventricular tachycardia induction in 2/21, 3/21, and 9/21 patients, respectively; b) aprindine + verapamil prolonged the cycle length of paroxysmal supraventricular tachycardia more than aprindine or verapamil alone; c) aprindine, verapamil, and aprindine + verapamil decreased the AV blocking rate by 15, 23, and 35 beats/min, respectively, in comparison with the control state; d) aprindine, verapamil, and aprindine + verapamil prolonged the effective refractory period of atrioventricular conduction system by 20, 34, and 76 msec, respectively, compared with the control state. In conclusion, aprindine + verapamil appear to be more effective than aprindine or verapamil alone in preventing paroxysmal supraventricular tachycardia with nodal reentry, but there was less benefit in those without nodal reentry (Wolff-Parkinson-White group).

[Effects of intravenous aprindine on hemodynamics in patients with cardiac dysfunction and its pharmacodynamics in patients with premature ventricular contractions].

The effects of aprindine, 100 mg iv, on hemodynamics, and the relationship between its inhibitory effect on PVC and its levels in the blood were determined in patients with diminished cardiac function. PVC was inhibited in 7 of 13 patients (54%), compared with a 50% inhibition rate in controls. The levels of aprindine in the blood after intravenous administration, rapidly decreased from 1.78 +/- 1.09 micrograms/ml immediately after administration, to 0.80 +/- 0.25 micrograms/ml after 15 min, to 0.65 +/- 0.23 micrograms/ml after 30 min and to 0.56 +/- 0.19 micrograms/ml after 1 hour. The duration of blood levels of 0.55 +/- 0.35 micrograms/ml, which are the levels presumed to be effective, was one hour after administration. The mean elimination half-life of aprindine was 18.9 +/- 8.4 hours. Aprindine produced relatively little effect on hemodynamics in patients with moderate to severe heart failure, but when its effects in individual cases were studied, it was found that aprindine elicited such changes as reduction in cardiac index, stroke volume index and stroke work index, and elevation in pulmonary arterial diastolic pressure. These findings suggest that care should be exercised in aprindine therapy in patients with diminished cardiac function. At least there should be monitoring of blood pressure and heart rate at appropriate times after intravenous administration.

Analysis of ventricular arrhythmias in patients with dilated cardiomyopathy--relationship between the effects of antiarrhythmic agents and severity of myocardial lesions.

In order to investigate the usefulness of antiarrhythmic drugs in patients with dilated cardiomyopathy (DCM), 42 patients with DCM were studied using 24 h ambulatory ECG monitoring, echocardiography and right ventricular endomyocardial biopsy. All 42 patients had ventricular arrhythmias with a Lown's classification of grade II or greater (grade IVb, 25; IVa, 7; III, 7; II, 3). The patients with grade IV arrhythmias tended to have greater dilating of the left ventricle and more pronounced interstitial myocardial fibrosis than patients with lower grades. Following procainamide and/or disopyramide treatment the severity of the ventricular arrhythmias improved in 12 (29%) of the 42 patients, did not change in 27 patients (64%), and deteriorated in 3 patients (7%). Treatment with aprindine or mexiletine was effective in 7 (50%) of the 14 patients who did not respond to procainamide and/or disopyramide. Although there were no significant differences in left ventricular dimension and contractility between patients in each group who did and did not respond to antiarrhythmic treatment, those who did respond had less interstitial myocardial fibrosis. Thus, in the procainamide and/or disopyramide treated group the percent interstitial fibrosis in responding vs nonresponding patients was 10.3 +/- 4.1% vs 18.7 +/- 8.3% (p less than 0.05) respectively, while in the group treated with aprindine or mexiletine these figures were 13.0 +/- 3.2% vs 26.1 +/- 7.9% (p less than 0.02), respectively. In conclusion, the effect of antiarrhythmic drugs in DCM was dependent on the severity of the pathological changes in the myocardium, and antiarrhythmic drugs should be appropriately used for the management of ventricular arrhythmias in DCM.