Recainam, a potent new antiarrhythmic agent: effects on complex ventricular arrhythmias.

The antiarrhythmic efficacy and safety of intravenous recainam, a newly synthesized compound displaying potent class I antiarrhythmic activity, were tested in 10 hospitalized patients with frequent (greater than 30/h) complex ventricular ectopic beats. There were seven men and three women of average age 57 years (range 21 to 74); five had ischemic heart disease, three had cardiomyopathy and two had valvular heart disease. Recainam was given as a 3.0 mg/kg per 40 min loading infusion followed by a 0.9 mg/kg per h maintenance infusion over a 24 hour observation period. Arrhythmia response was assessed both in the short term (comparing 2 hours before and 1 hour after drug loading) and in the long term (comparing 48 hours before drug loading and 23 hours of maintenance infusion). The median frequency of total premature ventricular complexes decreased in the short term by 99.6% (from 392.5 to 1.5/h, p less than 0.005) and in the long term by 99.7% (from 435 to 1.3/h, p less than 0.01). Repetitive beats were suppressed by a median of 100% both in the short term (p less than 0.006) and during 24 hour infusion (from 80.9 to 0/h, p less than 0.003). More than 90% suppression of repetitive beats occurred in all 10 patients (100%) and more than 90% suppression of total arrhythmias occurred in 9 patients (90%) during the maintenance period. Electrocardiographic PR and QRS intervals increased by 19% (p less than 0.001) and 24% (p less than 0.003), respectively, during therapy, but the JTc interval decreased (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of amiodarone on refractory ventricular fibrillation in acute myocardial infarction: experimental study.

OBJECTIVES: The aim of this study was to evaluate the efficacy of a single dose of intravenous amiodarone in facilitating defibrillation of ventricular fibrillation refractory to lidocaine and epinephrine plus direct current countershocks in experimental acute myocardial infarction. BACKGROUND: Amiodarone has been hailed as the most effective single antiarrhythmic drug for the treatment of ventricular arrhythmias. However, intravenous amiodarone has only sporadically been used in the defibrillation of ventricular fibrillation in acute myocardial infarction. METHODS: Acute myocardial infarction was induced in 60 dogs by ligation of the proximal left anterior descending coronary artery for 2 h. Animals that developed spontaneous ventricular fibrillation were treated with lidocaine and epinephrine plus five direct-current countershocks. Dogs with ventricular fibrillation refractory to this regimen were randomized to further treatment with additional intravenous administration of epinephrine and bolus lidocaine plus < or = 15 direct-current countershocks (group I) or administration of amiodarone, 10 mg/kg body weight intravenously, followed by defibrillation with direct-current counter-shock (group II). RESULTS: Sixteen (27%) of the 60 dogs in which the protocol was attempted developed spontaneous ventricular fibrillation 21 min after ligation and were included in the study. Lidocaine and epinephrine plus five direct-current countershocks succeeded in converting ventricular fibrillation in one dog (6%). The other 15 dogs were randomized to group I (8 dogs) or group II (7 dogs). Defibrillation was achieved in one of the eight dogs in group I and in six of the seven dogs in group II (p < 0.005). CONCLUSIONS: In an experimental model of acute ischemia, intravenous amiodarone (10 mg/kg) influences positively the response to defibrillation of ventricular fibrillation refractory to lidocaine and epinephrine plus direct current countershocks.

Outcome of patients with congestive heart failure treated with standard versus high doses of enalapril: a multicenter study. High Enalapril Dose Study Group.

OBJECTIVES: We sought to prospectively and randomly compare survival with clinical and hemodynamic variables in patients with congestive heart failure (CHF) treated with standard versus high doses of enalapril. BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors produce hemodynamic and symptomatic benefits in patients with CHF, but there is still controversy about the optimal dose in this clinical setting. METHODS: Two hundred and forty-eight patients with advanced CHF (age 56.3+/-12 years) were randomized to receive a maximal tolerated dose of enalapril, up to 20 mg/day in group 1 (mean dose achieved 17.9+/-4.3 mg/day, n = 122) and 60 mg/day in group 2 (mean dose achieved 42+/-19.3 mg/day, n = 126). RESULTS: At enrollment, patients in group 1 were in New York Heart Association (NYHA) functional class 2.6+/-0.7 and had a mean systolic blood pressure (SBP) of 117+/-18 mm Hg, a mean heart rate (HR) of 85+/-16 beats/min and a left ventricular ejection fraction (LVEF) of 20.0+/-9.8%. In group 2, patients were in NYHA class 2.6+/-0.7; their SBP was 118+/-17 mm Hg, HR 83+/-15 beats/min and LVEF 18.8+/-8.1%. There were no significant differences in these characteristics between the two groups of patients at enrollment. After 12 months of follow-up, 22 (18%) of 122 patients in group 1 and 23 (18%) of 126 patients in group 2 had died (p = 0.995, with 80% power of the study to detect a delta difference of 13%). The NYHA class was the same (1.9+/-0.7) in both groups; SBP was 111+/-16 and 111+/-17 mm Hg, HR 77+/-12 and 79+/-13 beats/min and LVEF 31+/-19% and 30+/-12% in groups 1 and 2, respectively. These differences were not statistically significant. The study had a power of 80% to detect (p = 0.05) the following changes: 13% in death rate, 0.25 units in NYHA class, 6 mm Hg in SBP, 5 beats/min in HR and 6% in LVEF. CONCLUSIONS: No significant differences were found in survival and clinical and hemodynamic variables between patients receiving standard and those receiving high doses of enalapril.

Efficacy of recainam, a new antiarrhythmic drug, for control of ventricular arrhythmias.

The antiarrhythmic efficacy and safety of oral recainam hydrochloride, a newly synthesized compound, were assessed during a 2-part study of 12 patients with frequent (at least 30/hour) ventricular premature complexes (VPCs). During the initial dose-ranging phase, 11 patients with qualifying arrhythmias (median VPC frequency 575/hour, range 37 to 1,494) received incremental oral doses of 100, 300 and 500 mg of recainam given every 8 hours, each for 3 days. Efficacy was assessed on the last day of each dose. The 300-mg/day dose of recainam was generally ineffective; the 900-mg/day dose was partially effective (58% median VPC reduction, p = 0.03); and the 1,500-mg/day dose was very effective (79% reduction, p less than 0.003). Median reductions in repetitive beats (beats in couplets and runs) for the 3 doses were 18% (difference not significant), 94% (p less than 0.01), and 98% (p less than 0.004), respectively. Recainam provided individual efficacy (at least 70% VPCs or at least 90% repetitive beat suppression, or both) in 7 (64%) of the patients taking 900 mg/day and in 8 (73%) taking 1,500 mg/day. Minimum steady-state plasma concentrations were higher in responders (1.8 +/- 0.5 microgram/ml) than in nonresponders (1.0 +/- 0.5 microgram/ml) (p less than 0.05). The electrocardiographic response to recainam (1,500 mg/day) included increases in PR (by 22%, p less than 0.003) and QRS (by 14%, p less than 0.002) intervals and a small decrease in JTc duration (by 9%, p less than 0.04). Radionuclide ejection fraction did not change. Noncardiac adverse reactions were minimal.(ABSTRACT TRUNCATED AT 250 WORDS)

Correlation and stability of heart rate and ventricular ectopy variability in patients with congestive heart failure.

The stability of indexes of heart rate variability and their possible association with spontaneous variability of ventricular ectopy was examined in 13 patients with advanced congestive heart failure over 14 consecutive days of 24-hour ambulatory electrocardiographic recording. It was found that time and frequency domain measures of heart rate variability are stable over time and are inversely correlated with spontaneous variability of ventricular ectopy.

Usefulness of d, I sotalol for suppression of chronic ventricular arrhythmias.

Sotalol is a unique beta-blocking drug, possessing significant class III antiarrhythmic activity. The efficacy and safety of 2 doses of sotalol (320 and 640 mg/day, divided in 2 doses) were compared to placebo in a 6-week randomized, double-blind, multicenter study of 114 patients with chronic ventricular premature complexes (VPCs) at frequencies of greater than or equal to 30/hour. Sotalol significantly reduced VPCs in patients receiving both low (n = 38) and high (n = 39) doses, compared with patients (n = 37) receiving placebo (by 75 and 88%, respectively, vs 10%; p less than 0.001, sotalol vs placebo; p less than 0.05, high vs low dose). The individual efficacy criterion (greater than or equal to 75% VPC reduction) was achieved in 34% of low-dose and 71% of high-dose sotalol versus 6% of placebo-treated patients (p less than 0.003, sotalol vs placebo; p = 0.007, high vs low dose). Repetitive beats were suppressed 25% by placebo (difference not significant), 80% by low-dose (p less than 0.003) and 78% by high-dose sotalol (p less than 0.005). Sotalol decreased heart rate (by 24 to 25%, p less than 0.001) and increased PR (by 4 to 6%, p less than 0.001) and corrected JT intervals (by 12 to 13%, p less than 0.001), but did not change ejection fraction. Proarrhythmia (nonfatal) occurred in 3 sotalol and in 2 placebo patients. Nine discontinued therapy because of adverse effects (1 low dose and 8 high dose, p less than 0.02). In summary, sotalol is an efficacious antiarrhythmic drug for VPC suppression; in lower doses, it is somewhat less effective but better tolerated.

Relation of dispersion of QRS and QT in patients with advanced congestive heart failure to cardiac and sudden death mortality.

This study examined the usefulness of 01 and QRS dispersion in the prognosis of patients with advanced congestive heart failure (CHF). One hundred four patients in New York Heart Association functional classes II to IV, with a left ventricular ejection fraction of <35%, and untreated with antiarrhythmic drugs, were followed prospectively. QRS and QT dispersion were defined as the maximum difference in QRS and QT interval duration, respectively, measured on all leads of standard 12-lead electrocardiograms. The end points of the study were non-sudden and sudden cardiac mortality. During an average follow-up of 20 months, there were 13 non-sudden and 10 sudden deaths. The average QRS duration was significantly longer in nonsurvivors than in survivors (125 ¿ 34 vs 113 ¿ 34 ms, respectively, p <0.04). Similar results were obtained with 01 dispersion (95 ¿ 48 ms vs 78 ¿ 31 ms, respectively, p <0.03) and QRS dispersion (54 ¿ 17 ms vs 46 16 ms, respectively, p <0.02). Furthermore, patients who died suddenly had significantly greater QRS dispersion than patients who survived (56 ¿ 13 vs 46 ¿ 16 ms, respectively, p <0.02). In a multivariate analysis, QT and QRS dispersion were both independent predictors of non-sudden cardiac death (p = 0.01 and p = 0.001, respectively), and QRS dispersion was also an independent predictor of sudden cardiac death (p = 0.04). Death rate in patients with 01 dispersion >90 ms was 2.8-fold higher than those with 01 dispersion 90 ms (95% confidence intervals [CI] 1.2 to 6.4). Similarly, the death rate in patients with QRS dispersion >46 ms was 3.9-fold higher than in those with QRS dispersion 46 ms (95% Cl 1.6 to 9.5). These findings suggest that QT and QRS dispersion are useful predictors of mortality in patients with advanced CHF. ¿2000 by Excerpta Medica, Inc.

Indium-111 monoclonal antimyosin cardiac scintigraphy in men with idiopathic dilated cardiomyopathy.

This study examined the prognostic value and the evolution of the heart-to-lung ratio of monoclonal antimyosin antibody (MAA) uptake in patients with a diagnosis of idiopathic dilated cardiomyopathy (IDC). Uptake of indium-111-labeled MAA occurs when the myocytes become irreversibly damaged. The study included 29 men with IDC followed up for 3 years. The diagnosis was verified by endomyocardial biopsy in all patients. Patients who survived beyond 1 year were restudied. Baseline heart-to-lung ratio of MAA was 1.74+/-0.22. Multivariate Cox regression analysis revealed that MAA and New York Heart Association class were independent predictors of late mortality, with a hazard ratio of 4.4 (95% confidence interval 1.1 to 17.9, p = 0.036) and 7.5 (95% confidence interval 2.0 to 28.4, p = 0.003), respectively, when heart-to-lung ratio of MAA uptake was > 1.74 and New York Heart Association class was >11. When these patients were divided into those with chronic IDC (group I [n = 19]) and those with subacute IDC (group II [n = 10]), baseline heart-to-lung ratio was 1.7+/-0.2 and 1.86+/-0.25, respectively (p = NS). In the surviving patients, on restudy, the heart-to-lung ratio of MAA uptake was unchanged in group I (1.64+/-0.20, p = NS), but had decreased to the level of group I (1.66+/-0.21 [p = 0.008]) in group II. Thus, men with IDC and a high heart-to-lung ratio of MAA uptake have a worse long-term prognosis than patients with a lower ratio. The heart-to-lung ratio of MAA decreases comparably over time in subacute IDC and remains stable in chronic IDC.

Effect of acute allograft rejection on exercise hemodynamics in patients who have undergone cardiac transplantation.

The effect of acute allograft rejection on exercise hemodynamics was evaluated in 8 consecutive cardiac allograft recipients (group 1) when the right ventricular endomyocardial biopsy showed evidence of allograft rejection (R), and when no evidence of rejection (NR) was present. A separate group of 10 cardiac transplant recipients (group 2) with no evidence of rejection on biopsy done at the end of the first and second year post-transplantation served as controls. The exercise hemodynamics were abnormal in both groups in both studies with a moderate increase of the pulmonary artery wedge pressure to a mean of 17.2 (NR) and 19.4 mm Hg (R) in group 1 (p = not significant [NS]) and 20.1 and 21.2 mm Hg in group 2 (p = NS), a mild increase of the mean right atrial pressure to a mean of 10 mm Hg (NR) and 10 mm Hg (R) in group 1 (p = NS), 11.9 mm Hg and 12.5 mm Hg in group 2 (p = NS), and a moderate increase of the arteriovenous oxygen content difference to a mean of 8.5 (NR) and 8.4 vol percent (R) in group 1 and 8.3 and 8.0 vol percent in group 2. No significant difference was observed between the two studies of the same group in any of the hemodynamic parameters except for the heart rate in group 1 (from 91 +/- 16 to 97 +/- 16 beats/min [p < 0.05] with and without evidence of allograft rejection, respectively). In conclusion, heart transplant recipients do not usually manifest further exercise hemodynamic deterioration during mild to moderate rejection.

Long-term intermittent dobutamine infusion combined with oral amiodarone improves the survival of patients with severe congestive heart failure.

STUDY OBJECTIVE: To evaluate the effects of long-term intermittent dobutamine infusion (IDI) with concomitant administration of low-dose amiodarone in patients with congestive heart failure (CHF) refractory to standard medical treatment. DESIGN: Prospective, interventional clinical trial. SETTING: Inpatient and outpatient heart failure clinic in a university teaching hospital. PATIENTS AND INTERVENTIONS: Twenty-two patients with CHF refractory to standard treatment who could be weaned from dobutamine therapy after an initial 72-h infusion were included in this study. The first 11 patients (group 1) were treated with IDI, 10 micromin, as needed (mean, once every 16 days, lasting for 12 to 48 h); the next 11 patients (group 2) received oral amiodarone, 400 mg/d, and IDI, 10 microg/kg/min, for 8 h every 7 days. MEASUREMENT AND RESULTS: There were no differences in baseline clinical, hemodynamic, and five biochemical characteristics between the two groups. The left ventricular ejection fraction was 13.5 +/- 4.5% in group 1 vs 15.5 +/- 4.9% in group 2 (mean +/- SD; p = 0.451); mean pulmonary capillary wedge pressure was 31.3 +/- 4.4 mm Hg vs 29.4 +/- 3.3 mm Hg (p = 0.316); serum creatinine was 1.9 +/- 0.4 mg/dL vs 1.6 +/- 0.5 mg/dL (p = 0.19); and serum Na was 139.6 +/- 6.2 mEq/L vs 138.4 +/- 3.1 mEq/L (p = 0.569). At 12 months of follow-up, 1 of 11 patients (9%) was alive in group 1 vs 6 of 11 patients (55%) in group 2 (p = 0.011). Furthermore, in group 2, the functional status improved significantly within the first 3 months of treatment, from New York Heart Association functional class IV to 2.63 +/- 0.5 (p = 0.0001). CONCLUSION: Long-term IDI in conjunction with amiodarone, added to conventional drugs, improved clinical status and survival of patients with severe CHF.

Redistribution of amiodarone in heart transplant recipients treated with the drug before operation.

Seven heart transplant recipients (six men and one woman) treated with oral amiodarone 194 +/- 100 mg/day before operation for a period of 30 +/- 48.5 months were studied. The myocardial concentrations of amiodarone in the transplanted heart peaked in the second posttransplantation week (87.6 +/- 80.7 microg/g myocardial tissue) and remained detectable in the twelfth week (10.2 +/- 8.4 microg/g myocardial tissue). The ratio of myocardial/plasma concentrations peaked at the end of the sixth posttransplantation week. In conclusion, amiodarone accumulated rapidly in the transplanted myocardium of heart transplant recipients treated with the drug before operation and remained detectable for at least 3 months.

The disposition of recainam hydrochloride during and after intravenous loading and maintenance infusion in cardiac patients.

Recainam hydrochloride is a newly synthesized propylurea compound demonstrating potent antidysrhythmic effects. Recainam was administered as a loading dose of 3 mg/kg/40 minutes followed by a continuous infusion of 0.9 mg/kg/hr for 23 hours and 20 minutes to ten patients with cardiac disease and frequent PVCs (more than 30/hr). A total of 15 plasma samples were drawn over 36 hours during and after the infusion. Plasma recainam concentration was determined by high performance liquid chromatography (HPLC). The mean (+/- SD) postload and 24-hour plasma concentrations were 5.19 +/- 0.51 and 3.41 +/- 0.71 micrograms/mL, respectively. The data were best described by a two-compartment model yielding the following mean (+/- SD) pharmacokinetic parameters: lambda 1 = 2.62 +/- 0.68 hr-1, lambda 2 = 0.144 +/- 0.014 hr-1, t1/2 lambda 2 = 4.84 +/- 0.46 hr, CLT = 0.268 +/- 0.057 L/hr/kg, CLR = 0.143 +/- 0.052 L/kg/hr, CLNR = 0.125 +/- 0.041 L/hr/kg, Vdss = 1.3 +/- 0.19 L/kg, and Vd lambda 2 = 1.9 +/- 0.43 L/kg. There were no adverse reactions. Based on these data, recainam can be safely administered as a loading dose followed by a continuous infusion in patients with stable cardiac disease without significant ventricular dysfunction.

Comparison of Fick and dye cardiac outputs during rest and exercise in 1,022 patients.

The Fick and indicator-dilution techniques for measurement of cardiac output (CO) were compared at rest in 1,022 patients and in 786 during exercise. Duplicate measurements of dye CO at rest revealed that 92.7% fell within 10% of the line of identity and 99% within 20%. For the resting Fick and dye comparisons, 44.6% were within 10% of the identity line and 74.7% within 20%. When mean CO was less than 4.4 L/min, dye CO was higher than Fick. This relationship persisted for CO between 4.4 and 7.4 whereas for above 7.4 L/min, Fick was higher than dye. During exercise, 50.2% of the Fick and dye comparisons fell within 10% and 77.1% within 20% of the line of identity. There was a systematic difference between the two methods during exercise with dye CO higher than Fick CO. This study agrees with Fick and dye comparison studies with 74.7% and 77.1% of values within 20% of the identity line during rest and exercise, respectively. However, these results differ from others in that dye CO was higher than Fick CO for low and normal values whereas Fick was greater for the higher CO values. The overall agreement between the two methods in a large group of patients with diverse cardiac diseases over a broad spectrum of CO values supports use of either method for clinical studies.

High incidence of clinical and subclinical toxicity associated with amiodarone treatment of refractory tachyarrhythmias.

Amiodarone has been hailed as the most effective single antiarrhythmic drug for treatment of refractory supraventricular and ventricular arrhythmias. However, questions continue to arise about its long-term potential toxicity and true efficacy rates. We, therefore, reviewed our experience with 78 patients, mean age 59 +/- 14 years, with drug refractory tachyarrhythmias treated with amiodarone. Sixty-two patients were treated for recurrent ventricular tachycardia or ventricular fibrillation, 4 for complex ventricular ectopy and 12 for supraventricular tachyarrhythmias. Patients have been treated for a mean of 9.9 months (range, 1 day to 39.1 months); 34(55%) continued to be successfully treated for ventricular tachycardia/ventricular fibrillation, 2 (50%) for complex ventricular ectopy and 5 (42%) for supraventricular tachyarrhythmias. Amiodarone toxicity was frequent, occurring in 57/72 patients (79%) who were treated for more than one week. Adverse effects led to drug discontinuation in 15 (21%), 3 because of pulmonary toxicity (1 in combination with neuropathy and another with drug-induced hepatitis); 2 because of chemical hepatitis; 1, confusion; 6, neuropathy; 2, arrhythmia exacerbation; 2, symptomatic bradycardia; and 1 because of impotence. Of the 62 ventricular tachycardia/ventricular fibrillation patients who were treated with amiodarone, 8 (13%) expired: 4 died suddenly and 4 from documented ventricular tachycardia during treatment. In contrast, of 16 patients who had discontinued amiodarone because of initial adverse effects or drug failure and were treated with alternative antiarrhythmic medications, 5 (31%) died suddenly. In conclusion, amiodarone appears to be fairly effective in high risk patients with refractory cardiac tachyarrhythmias but results in a rather high incidence of adverse effects in long-term follow-up.(ABSTRACT TRUNCATED AT 250 WORDS)

Spontaneous variability of ventricular arrhythmias in patients with chronic heart failure.

Spontaneous variability of ventricular arrhythmia in patients with chronic heart failure is not well described. We measured this variability in 23 consecutive patients with chronic heart failure who were prospectively enrolled in the placebo limb of a trial concerned with treatment of heart failure. Patients underwent from one to three periods of ambulatory monitoring separated by 1 to 3 months while they were not receiving antiarrhythmic drug treatment. The variability in frequency of premature ventricular complexes (PVCs) was determined at interrecording intervals of 1, 2, and 3 months. The percentage reductions in total PVCs required to exceed the 95% confidence limits of spontaneous variability at these intervals were 91%, 90%, and 97%, respectively. Corresponding values for repetitive beats (beats in couplets and beats in ventricular tachycardia events) were 98%, 80%, and 97% and for ventricular tachycardia events 98%, 83%, and 98%, respectively. The percentage increases in total PVCs, repetitive beats, and ventricular tachycardia events required to identify aggravation of arrhythmia in this study population were 1301%, 4050%, and 6147%, respectively, at 1-month intervals and 2950%, 2868%, and 5938%, respectively, at 3-month intervals. The percentage reductions required to show a true drug effect at 2- and 3-month intervals were 63% and 84% for patients with an ejection fraction less than 0.22 and 89% and 98% for those with an ejection fraction greater than or equal to 0.22 (p less than 0.05 for both). Ventricular arrhythmia would have been missed in 6 (26%) of the 23 patients if only one screening ambulatory recording was available. Thus marked variability in PVCs occurs in patients with chronic heart failure.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-DR typing and lymphocyte subset evaluation in rheumatic heart disease: a search for immune response factors.

Several autoimmune diseases have been associated with increased frequencies of specific histocompatibility (HLA) antigens, particularly for the D (DR) locus, that may be linked to immune response genes. Rheumatic valvular heart disease (RHD) has been postulated to have autoimmune features, but HLA associations have not been established. We, therefore, performed HLA-DR typing in 33 consecutive patients with RHD and in 82 normal blood bank control subjects. We also evaluated the frequencies of lymphocyte subsets by means of monoclonal antibodies and immunofluorescence flow cytometry and made functional correlations for the natural killer cell (NKC) in patient subsets. The DR patterns in RHD were heterogeneous. However, significant differences were noted for DR4 and DR6. DR4 was present in 52% (17 of 33) of RHD patients vs 32% (26 of 82) of control subjects (p less than 0.05). DR6 was present in 6% (2 of 33) of patients vs 26% (21 of 82) of control subjects (p less than 0.02). The associated relative odds of DR4 was 2.3 and the etiologic fraction was 0.30. The relative odds of DR6 was 0.19 and the preventive fraction was 0.21. A distinct clinical profile was not associated with DR4 positivity or DR6 negativity. The frequency of lymphocyte subsets was not significantly changed except for OKT8. Median NKC numbers tended to be higher in RHD patients than in control subjects (p less than 0.05). In contrast, NKC functional activity tended to be lower in RHD; median lymphocyte to target cell (K562 line) ratio resulting in 50% killing (L/T 50) was 20.5 in RHD patients vs 11.5 in control subjects (p = 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in spontaneous variability of ventricular ectopic activity as a function of time in patients with chronic arrhythmias.

Previous determinations of spontaneous variability in ventricular arrhythmia have often been based on measurements from consecutive days in small patient populations, whereas clinical determinations of drug efficacy typically compare measurements at intervals of 1 week and longer to baseline. We, therefore, sought to determine whether spontaneous arrhythmia variability changes as a function of time during periods ranging from 1 day to 1 year or longer. The percent reduction in the frequency of total premature ventricular complexes (PVCs) and repetitive ventricular beats required to show true drug effect rather than spontaneous variability in PVCs was determined in 47 consecutive patients with chronic ventricular arrhythmias who underwent multiple ambulatory monitor recordings while off active drug treatment (during placebo therapy). The variability in PVC rate was determined during the intervals of 1 day, 1 week, 2 weeks, 3 weeks, 4 weeks, and 1 year or longer. The percent reductions in total PVCs required to exceed the 95% confidence limits of spontaneous variability at these intervals were 55%, 85%, 86%, 93%, 96%, and 96%, respectively. Corresponding values for repetitive beats were 75%, 95%, 92%, 95%, 94%, and 98%, respectively. The percent increase in total PVCs and repetitive beats required to establish "arrhythmia aggravation" caused by an antiarrhythmic drug with a 95% confidence limit also was calculated for this study population and was 124% and 303%, respectively, at 1-day intervals and 2,269% and 4,091%, respectively, at 1-year (or longer) intervals for the 24-hour monitor recordings. Variability was not substantially affected by underlying heart disease or ejection fraction. PVC rate showed a modest negative correlation with variability (r = 0.3). Thus, variability is substantially greater at 1 week, the usual time for clinical assessment of antiarrhythmic drug efficacy, than at 1 day (p less than 0.01). Suppression of more than 85% of total PVCs and more than 95% of repetitive beats appears to be necessary after 1-2 weeks to be confident of a true drug effect. Even greater variability is observed after 1 month and up to 1 year so that reductions of up to 95% in total PVCs and 98% in repetitive beats may represent spontaneous change.(ABSTRACT TRUNCATED AT 400 WORDS)

Initial and long-term outpatient experience with lorcainide for suppression of malignant and potentially malignant ventricular arrhythmias.

There is a need for effective, well-tolerated antiarrhythmic agents, particularly those effective by both intravenous and oral routes. Lorcainide, a new antiarrhythmic drug with such properties, was given long-term orally to 24 patients controlled initially with intravenous therapy--19 with frequent (greater than 1/min) complex premature ventricular complexes (PVCs) on a baseline 24-hour Holter monitor and five with ongoing sustained ventricular tachycardia (VT) or frequent paroxysmal sustained VT, for a mean of 13 months (range 0.03 to 39.4 months). Long-term lorcainide was given in divided doses of 200 to 800 mg/day (median 260, mean 269 +/- 90 mg/day). Response to long-term lorcainide therapy was assessed at a mean of both 26 days and 12.2 months. Frequency of PVCs on baseline averaged 13,490/24 hours (median 10,578, range 2,115 to 61,716); couplets averaged 309/24 hours (median 166, range 0 to 5,686), and runs averaged 33/24 hours (median 30, range 0 to 2,951). Median frequency of PVCs decreased by 94% (p much less than 0.001) and 97% (p less than 0.01) at the first and second lorcainide efficacy assessments, respectively. Couplets decreased by a median of 99% (p much less than 0.001) and 100% (p less than 0.005) at the first and second assessments, respectively. Runs were suppressed by a median of 100% at both evaluations (p much less than 0.001). Only three (16%) of the patients with complex PVCs failed to respond to therapy. No recurrence during lorcainide has been noted in the five patients with ongoing sustained VT or recurrent episodes of VT.(ABSTRACT TRUNCATED AT 250 WORDS)

Intravenous amiodarone decreases the duration of atrial fibrillation associated with acute myocardial infarction.

PURPOSE: Atrial fibrillation (AF) is a fairly common complication of acute myocardial infarction (AMI). The aim of this study was to examine the safety and efficacy of intravenous amiodarone in converting AF associated with AMI. METHODS: Seventy patients with AMI complicated with AF were prospectively divided into 3 groups: a) In group D (n = 26), 0.75 mg digoxin was administered intravenously and thereafter as needed, b) In group AM (n = 16), 300 mg of amiodarone was infused over 2 hours followed by 44 mg/hour for up to 60 hours or until sinus rhythm was restored, c) In group D + AM (n = 28), 0.75 mg of digoxin was administered (as in group D) for the initial 2 hours followed by amiodarone infusion as in group AM. RESULTS: Sinus rhythm was restored: a) by the end of the 2nd hour in 9/26 patients from group D, 4/16 from group AM, and 10/28 from group D + AM (p = NS), b) by the end of the 96th hour, in 18/26 patients from group D, and in all patients from group AM and groupd D + AM. The corresponding duration of AF was 51 +/- 34 hours, 17 +/- 15 hours and 9 +/- 13 hours, respectively (F = 15.4, p < 0.001). AF recurred in 9/26, 5/16 and 1/28 patients of groups D, AM and D + AM, respectively (p = 0.026). The required dosage of amiodarone was lower in the D + AM group than in the AM group (603 +/- 563 mg versus 1058 +/- 680 mg, p = 0.037). CONCLUSIONS: Intravenous amiodarone was well tolerated in patients with AMI complicated by AF and was effective in decreasing the duration of AF. However, the combination of amiodarone and digoxin was superior to amiodarone alone in restoring sinus rhythm faster, maintaining sinus rhythm longer, and allowing the use of a lower cumulative amount of amiodarone.