[Comparative study of cibenzoline and flecainide by oral route for preventing recurrence of paroxysmal atrial tachyarrhythmias]. / Etude comparative de la cibenzoline et du flécaïnide administrés par voie orale dans la prévention de récidive des tachyarythmies auriculaires paroxystiques.

Although paroxysmal atrial arrhythmias are the commonest form of arrhythmia, their therapeutic management still remains controversial. Seventy one patients were included in a multicentre, randomized double-blind, double-placebo study, in parallel groups (37 in group C and 34 in group F) to compare the efficacy of cibenzoline (C) and flecainide (F), administered orally, in the prevention of recurrent atrial arrhythmia. The arrhythmia usually consisted of atrial fibrillation (n = 65), while 6 patients presented with paroxysmal atrial flutter. The mean daily dosages were 221 +/- 60 mg (C) and 165 +/- 49 mg (F). The mean age was 63 +/- 12 years in group C and 63 +/- 16 years in group F. In this trial, atrial arrhythmia was idiopathic in almost two-thirds of cases. The duration of follow-up of this study was 6 months, during which recurrences of arrhythmia were evaluated in terms of the symptoms experienced and in terms of ECG and Holter examinations repeated at the 3rd and 6th months. Supplementary ECG and Holter examinations were also performed in the presence of a clinical suspicion of recurrent symptoms. Comparison of the percentages of patients not developing a documented recurrence and who tolerated treatment, by Kaplan-Meler curves, showed a significant difference between cibenzoline (58%) and flecainide (56%). In the not-responders, the mean time to recurrence was 75 +/- 48 days in group C and 75 +/- 62 days in group F(NS). Six patients dropped out of the trial because of adverse events, including 3 cardiac adverse events (2 case of ventricular proarrhythmic activity). Four extracardiac adverse events led to discontinuation of treatment in group C. In conclusion, the efficacy of cibenzoline and flecainlde in the secondary prevention of atrial arrhythmia was found to be comparable, with 58% and 58% of patients in sinus rhythm, respectively, with a follow-up of 6 months.

Ventricular arrhythmia factors in mitral valve prolapse.

To assess the prevalence of ventricular arrhythmias and late potentials (LPs) in mitral valve prolapse (MVP) and to identify clinical, ECG, and echocardiographic markers of spontaneous ventricular arrhythmias, we studied 58 consecutive patients (mean age 46.6 +/- 17.8 years; 29 males, 29 females) with MVP diagnosed by echocardiography. Patients underwent ambulatory ECG recording (n = 58), exercise stress test (n = 56), signal-averaged ECG (n = 58), and programmed ventricular stimulation (n = 52). Ten patients (17.2%) had spontaneous nonsustained ventricular tachycardia (NSVT), 26 patients (44.8%) had premature ventricular contractions (PVCs), Lown grade > or = 3 during 24-hour ECG, and 19 had Lown grade > or = 3 PVCs during exercise stress test; 13 patients had LPs (22.4%). We provoked sustained VT in one case and NSVT in ten cases. Patients with complex ventricular arrhythmias during 24-hour ECG and exercise stress test were older and more often had mitral regurgitation. There was a statistical correlation between the presence of LPs and spontaneous VT (46.1% vs 8.9%; P < 0.005) and induced ventricular arrhythmias (50% vs 12.8%; P < 0.005). No correlation was found between spontaneous ventricular arrhythmias and thickness or posterior displacement of the mitral valve. In conclusion, complex ventricular arrhythmia (especially VT) and LPs are frequent in MVP. Patient age and mitral regurgitation seem to be determinant factors of complex ventricular arrhythmias in MVP. On signal-averaged ECG, absence of LPs seems to be a good additional marker to identify MVP patients without spontaneous VT. On the other hand, programmed ventricular stimulation does not appear valuable in determining a MVP subgroup with a high risk of ventricular arrhythmias.

[Injectable and oral cibenzoline in the treatment of supraventricular tachycardia related to intranodal reentry or accessory atrioventricular conduction pathway]. / Etude de la cibenzoline injectable et orale dans le traitement des tachycardies supraventriculaires liées à une rentrée intranodale ou à une voie de conduction auriculo-ventriculaire accessoire.

Cibenzoline, a Vaughan-Williams Class I antiarrhythmic agent, was studied in 26 patients with orthodromic supraventricular tachycardia (SVT) by nodal reentry (n = 10) or an accessory pathway (AP) (n = 16). IV cibenzoline accelerated sinus rhythm, prolonged PR, AH, HV and QT, widened QRS and depressed or blocked anterograde and retrograde conduction in the accessory pathway, significantly, without significantly modifying conduction capacity in the AV node, nor atrial, nodal or ventricular refractory periods. It converted 6/10 of nodal reentries and 9/16 of reentries due to an AP, by a mean dose of 1 mg/kg, in 2 to 3 minutes, in 12 cases out of 16 by blocking retrograde conduction in the reentry circuit. It prevented reinduction of 12 of the 26 cases of SVT, significantly slowing the cycle of induced SVT in other patients. Oral cibenzoline (260 to 390 mg/day) prevented induced SVT in 11 cases out of 25 and spontaneous SVT in 14 cases out of 26, with a follow-up of 11 +/- 4 months (6 to 16), and this regardless of the reentry mechanisms. Intravenous cibenzoline was not associated with any clinical or hemodynamic intolerance but there was facilitation of episodes of SVT in one patient. Oral administration caused only one case of digestive intolerance, leading to lowering of the dose. Plasma levels showed no significant differences between successes and failures, for both the injection and oral formulations of cibenzoline, whether in terms of the conversion or prevention of episodes. Electrophysiological investigations had a 60% positive and 50% negative predictive value, a sensitivity of 64% and a specificity of 50%. Cibenzoline thus appears to be useful for the conversion and prevention of episodes, SVT, regardless of the reentry circuit, and seems justified, in view of its good safety/acceptability, as first line treatment in this diagnostic indication, measurement of plasma levels and electrophysiological investigations being of little apparent value in terms of guiding treatment and predicting its results.

[Drug-induced ventricular tachycardia]. / Les tachycardies ventriculaires d'origine médicamenteuse.

Certain drugs can induce ventricular tachycardia (VT) by creating reentry, ventricular after potentials or exaggerating the slope of phase 4. These may or may not be symptomatic, sustained or non-sustained and have variable ECG appearances: monomorphic or polymorphic, bidirectional, torsades de pointes. They risk degenerating into ventricular flutter of fibrillation and have been held responsible for the increased mortality observed unexpectedly in some long-term treatments. The drugs responsible are mainly those used in cardiology, probably due to predisposing circumstances (cardiomegaly, cardiac failure, previous severe ventricular arrhythmias, therapeutic associations, metabolic abnormalities). These include primarily the antiarrhythmic drugs (IA, IC, sotalol and bepridil), digitalis, sympathomimetics and phosphodiesterase inhibitors. These complications may be toxic or idiosyncratic, in patients with or without cardiac disease, and may also occur with other drugs: vasodilators and anti-anginal drugs (lidoflazine, vincamine, fenoxedil), psychotropic agents (phenothiazine and imipramine), antimitotics, antimalarials (chloroquine) or antibiotics (erythromycin, pentamidine). The prognosis is severe and the treatment is often difficult which makes prevention, helped by repeated surface ECG (or Holter monitoring), very important with careful assessment of patients at risk.

[Preventive drug therapy of recurrence of atrial fibrillation]. / Prévention médicamenteuse des récidives de fibrillation auriculaire.

Without treatment, about 60% of atrial arrhythmia patients suffer a relapse within 3 months and 70% within one year. Antiarrhythmic treatment intended to reduce this percentage is therefore justified, on condition that it is well tolerated. Several preliminary questions have to be settled before this medical prophylaxis: 1) Justification of antiarrhythmic treatment (sometimes pointless to deal with very occasional episodes); 2) Treatment of the underlying heart disease (valve disease, cardiothyrotoxicosis, etc.) or promoting factors (potassium depletion etc.); 3) Accurate assessment of any associated conduction abnormalities, which may constitute a contraindication to antiarrhythmic treatment (WPW syndrome in the case of verapamil and the digitalis-like drugs) or require additional treatment (pacemaker); 4) Definition of the mechanism (vagal or sympathotonic) inducing arrhythmia; 5) Evaluation of the hemodynamic parameters of the underlying heart disease (size of the atria, ventricular function, coronary or valvular lesions) which may limit the efficacy of the treatment. Once these parameters have been identified, the primary treatment should be type la or lb antiarrhythmics, which have been shown to be effective, despite the fact that they are not without arrhythmic risks (the Ib antiarrhythmics are less effective and have a poor safety profile). The beta-blockers have preferential indications (hypersympatheticotonia, hyperthyroidism, hypertrophic myocardiopathy, mitral prolapse, angina etc.) and can be replaced by verapamil or bepridil if there are non-cardiac contraindications (ulcers, asthma, diabetes). Amiodarone is extremely effective, but its poor extracardiac safety restricts its long-term use. Complementary treatments (digitalis-like, anticoagulants or anti-PAF and cardiostimulant drugs) should be added if necessary. Recurrences (to be confirmed by ECG or Holter) should lead to rigorous confirmation of therapeutic compliance and observance of simple hygienic and dietary measures (no excessive exertion, elimination of stimulants etc.). With strict clinical and ECG monitoring, it would then be possible either to increase the dose levels (accompanied by plasma determinations if possible) or to switch to a treatment with more effective, but more aggressive drugs (amiodarone, flecainide) or to use drug associations (la and lb, la and II etc.). Repeated failure of such attempts should lead to a non-medical approach to treatment.

[Prevalence of atrial arrhythmia in 48 hypertensive patients: research of predictive criteria]. / Etude de la prévalence des troubles du rythme auriculaire chez 48 patients hypertendus: recherche de critères prédictifs.

UNLABELLED: We studied atrial arrhythmias during a continue prospective work in 48 hypertensive patients referred to the OMS criteria. Hypertension was confirmed by a blood pressure ambulatory monitoring and stress testing blood pressure trend. All cardiovascular drugs were stopped at admission. Patients with associated valvular or coronary artery disease were excluded from analysis. In all patients, we realized a twelve lead-ECG, stress testing, 24 hour Holter monitoring, a blood pressure ambulatory monitoring, two-dimensional echocardiography with Doppler study and cardiac radio-nuclide angiography with diastolic function study. Atrial arrhythmias were considered significant if more than 100 premature atrial beats (PAB) and/or more than three successive PAB were present during Holter monitoring. Significant atrial arrhythmias were found in 39.5% of patients (group II, n = 19), not significant in 60.5% of patients (group I, n = 29). The duration of hypertension was longer in group II (140 vs 66 months, p < 0.05). There was no difference between the two populations considering left atrial size or blood pressure level. Furthermore, we were surprised to find a normal E/A ratio on mitral Doppler recording in patients with atrial arrhythmias (1.23 vs 0.9; p < 0.05). Others diastolic parameters didn't significantly differ. Left ventricular mass index was similar in the two groups but patients with atrial arrhythmias had more asymmetric hypertrophy (1.23 vs 1.13 septum/posterior wall ratio: p < 0.05). CONCLUSION: atrial arrhythmias in our study seem to be more dependent from duration of HTA and left ventricular asymmetric structure than from left atrial size.(ABSTRACT TRUNCATED AT 250 WORDS)