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  • 1
    Electronic Resource
    Electronic Resource
    Springer
    Journal of interventional cardiac electrophysiology 4 (2000), S. 57-63 
    ISSN: 1572-8595
    Keywords: electrophysiologic study ; ventricular tachycardia ; ventricular fibrillation ; sotalol ; beta-block
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Arrhythmic death can be reduced by antiarrhythmic drugs to a range of 2—4%. Electrophysiologic study by testing noninducibility of ventricular arrhythmia represents the classic method for evaluating the effectiveness of drug therapy. Several clinical studies have shown thaat sotalol suppresses VT induction and prevents arrhythmias recurrences at long term follow-up in 23% to 67% of patients. The efficacy of sotalol EP guided therapy in preventing VT/VF is not necessarily related to prevention of sudden death. In the ESVEM study the superiority of d,l-sotalol to other antiarrhythmic drugs was confirmed. The response to programmed ventricular stimulation was found to be strongly predictive for arrhythmia free state while the failure of sotalol therapy to suppress VT at the EP study was associated with an high recurrence rate (40%). However, EP study failes to predict freedom from sudden death. The beta-blocking activity of racemic sotalol may account for some of the observed survival benefit. Beta-blockers therapy reduces mortality in patients after myocardial infarction primarily by a reduction of sudden death. A reduction of death, worsening heart failure and life threatening ventricular arrhythmias was shown in a recent study on carvedilol. In the prospective study of Steinbeck the EP guided-therapy did not improve the overall outcome when compared to metoprolol. Suppression of inducible arrhythmias by antiarrhythmic drugs was associated with a better outcome. The effectiveness of defibrillator therapy in reducing overall mortality, has been uncertain since great clinical trials have been concluded. MADIT, AVID and CASH trials confirmed the superiority of ICD therapy over antiarrhythmic drugs therapy: ICD should be considered the first choice therapy in post-cardiac arrest patients. The ongoing BEST Trial will give us further responses about the interaction between EP study and metoprolol effect compared to ICD in patients post myocardial infarction also focusing on tolerability and compliance of the beta-blocking therapy in patients with low ejection fraction. In this study will be useful to optimize therapy in patients at high risk of sudden death
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1573-7241
    Keywords: antiarrhythmic therapy ; pharmacokinetics ; propafenone ; ventricular premature beats
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary We evaluated the antiarrhythmic efficacy and the minimal effective concentrations of propafenone and its metabolite 5-hydroxy-propafenone during a) acute intravenous infusion (1.5 mg/kg in bolus followed by 45 minutes infusion), b) an acute oral single-dose test (450 mg), and c) 14-day chronic therapy (300 mg tid) followed by a washout. Oxidative metabolism was assessed by a debrisoquine oral test in every patient. Eleven patients with stable ventricular premature beats (VPBs)≥300/hr and Lown class ≥ 3 completed the study. The main results emphasized a certain discrepancy between the clinical effect of the acute intravenous infusion (efficacy in 5 out of 11 patients) and of the acute oral test and chronic therapy (efficacy in 11/11), with a time lag of the ECG changes during the acute intravenous infusion. The minimal effective concentrations were lower after acute oral administration compared with chronic treatment both for propafenone (200±189 ng/ml vs. 492±530 ng/ml; p〈0.05) and for 5-hydroxy-propafenone (82±40 ng/ml vs. 149±80 ng/ml; p〈0.02). A linear correlation was demonstrated between drug/metabolite ratios of propafenone and debrisoquine, either after acute oral (r=0.91) or after chronic administration (r=0.84). The pharmacokinetics of propafenone was nonlinear and showed wide interindividual variations. In conclusion, a) the lower efficacy and delayed electrophysiologic effects of propafenone after intravenous administration suggest that longer infusion times are necessary for complete antiarrhythmic efficacy; b) the differences observed in the minimal effective concentrations of acute versus chronic oral therapy suggest the development of partial tolerance to propafenone during chronic treatment.
    Type of Medium: Electronic Resource
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