Maria I. Anastasiou-Nana

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.

Long-term experience with sotalol in the treatment of complex ventricular arrhythmias

Sotalol was given for extended therapy to 22 of 29 patients with frequent (greater than or equal to 30/hour) complex premature ventricular complexes (PVCs) who had participated in a short-term study of sotalol vs placebo. Open-label sotalol was given in individually titrated divided doses of 160 to 800 mg/day (median 323, mean 386 mg/day). Response was assessed at approximately 1, 6, and 12 months or until patient discontinuation. The period of sotalol therapy averaged 9 months (range, 0.2 to 22.7). At about 1 month, 13 (59%) of 22 patients showed effective control of arrhythmia. The median percentage change in total PVCs for individual patients at 1 month was -70% and for repetitive PVCs it was -95%. At about 6 months, 10 (45%) of the 22 patients continued to be successfully treated; at about 12 months, seven patients continued on sotalol, six (27%) successfully treated according to Holter criteria. Reasons for discontinuation included lack of efficacy in nine, adverse effects in four (fatigue in three, bradycardia with sinus pauses in one), and miscellaneous reasons in two. ECG PR and especially QTc intervals increased significantly during therapy (p less than 0.02, p less than 0.01, respectively). In summary, sotalol is a moderately effective antiarrhythmic agent in patients with complex PVCs, but during long-term therapy a rather high dropout rate was observed because of arrhythmia recurrence or adverse effects.

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)

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)

Comparison of intravenous lorcainide with lidocaine for acute therapy of complex ventricular arrhythmias: Results of a randomized study with crossover option

There is a need for effective, well tolerated, intravenous antiarrhythmic agents. The effects of lorcainide, a new class I antiarrhythmic agent, were compared with those of lidocaine in a randomized parallel study with cross-over option in 30 hospitalized patients with frequent (greater than 1/min) complex ventricular arrhythmias. Lorcainide loading dose was 2 mg/kg (at 2 mg/min) supplemented, if needed, with 100 mg in 1 hour; maintenance dose was 8 mg/h. Lidocaine loading dose was 1 mg/kg (at 25 mg/min) supplemented, if needed, with 50 mg in 2 minutes; maintenance dose was 2 or 3 mg/min (as needed). Arrhythmias were compared for 2 hours before and after drug loading. Initially responding patients (minimum of 70% arrhythmia suppression) were continued on maintenance therapy for 24 hours. Patients initially failing or with later arrhythmia escape crossed over to alternating therapy (seven to lidocaine, nine to lorcainide). The median frequency of premature ventricular complexes decreased by 76% after lidocaine (p less than 0.05) and by 93% after lorcainide (p less than 0.001); this difference approached significance (p = 0.06). More than 95% arrhythmia suppression was achieved by lorcainide in 47% of patients and by lidocaine in only 13% (p less than 0.05). Couplets decreased by a median of 100% after lorcainide and by 89% after lidocaine. Couplets were eliminated in 62% of the patients after lorcainide and in 27% after lidocaine (p = 0.06). There was 100% suppression of runs of premature beats in 11 patients after lorcainide and 99% suppression in 10 patients after lidocaine.(ABSTRACT TRUNCATED AT 250 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)

Quantification of Prevalence of Asymptomatic Ventricular Arrhythmias in Patients with Heart Failure

Ventricular arrhythmias (VAs) are recorded in many patients with chronic heart failure. The present study was designed to prospectively determine and quantify the prevalence of asymptomatic VAs in this patient population.

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 μg/mL, respectively. The data were best described by a two‐compartment model yielding the following mean (± SD) pharmacokinetic parameters: λ1 = 2.62 ± 0.68 hr−1, λ2 = 0.144 ± 0.014 hr−1, t1/2 λ2 = 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 Vdλ2 = 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.

Spontaneous Variability of Ventricular Ectopic Activity in Patients with Sustained Ventricular Tachycardia and in Survivors of Cardiac Arrest

Background: Spontaneous variability of ventricular arrhythmia has been described in patients with chronic stable ventricular arrhythmias and in patients with chronic heart failure. However, no data are available on spontaneous variability in patients with sustained ventricular tachyarrhythmias. Thus, the present study was designed to prospectively determine the extent of spontaneous variability of ventricular arrhythmia in patients with sustained ventricular tachyarrhythmias and in survivors of cardiac arrest.