Oral flecainide for prophylaxis of paroxysmal atrial fibrillation.

This study was designed to assess the clinical efficacy of oral flecainide for the prevention of paroxysmal attacks of atrial fibrillation (AF). Forty patients with frequent, very symptomatic AF were selected for study; 31 had vagally induced AF. All patients were considered to be drug resistant. Each had recurrences of AF despite previous antiarrhythmic therapy that included high doses of amiodarone given alone or in combination with a class IA antiarrhythmic agent. In 6 patients, very high doses of amiodarone were efficacious in the prevention of AF; however, the doses had to be reduced because of adverse effects, which resulted in the recurrence of the arrhythmia. Patients were followed up for a period of 18 months and assessed by both symptom development and Holter monitor recordings. Patients received flecainide at an initial dose of 300 mg/day, which was increased to 400 mg/day in case of failure. If the initial dose was successful, the dose was reduced until the lowest one required to prevent recurrences of the arrhythmia was found. Amiodarone was also reduced or withdrawn whenever possible. The results show that AF in 32 of 40 patients was controlled with flecainide given alone (11 of 32) or in combination with amiodarone (21 of 32). Only 8 patients were considered to be drug resistant. The mean dose required to prevent recurrences of AF was also determined for each drug. The combined administration of flecainide and amiodarone allowed a significant reduction in the daily dose of amiodarone (p less than 0.005). On the other hand, daily doses of flecainide given with or without amiodarone were not significantly different (204 vs 209 mg/day).(ABSTRACT TRUNCATED AT 250 WORDS)

Flecainide in quinidine-resistant atrial fibrillation.

Flecainide (100 mg twice daily) was used for prevention of paroxysmal atrial fibrillation (PAF) in 52 patients with frequent symptomatic attacks that were resistant or intolerant to quinidine (600-900 mg/day). Underlying heart disease was present in only 8 cases and left ventricular ejection fraction was always greater than 30%. No patient had had a myocardial infarction. Vagally induced PAF was clinically documented in 35 patients. Amiodarone, previously used and ineffective, was combined with flecainide in 33 patients. After 1-5.8 years of follow-up, complete disappearance of PAF was observed in 38 patients (73%). The success rate was slightly higher in patients with vagally induced PAF (p = 0.07). Extracardiac side effects necessitated withdrawal in only 3 cases. Permanent pacemaker was needed in 7 patients on amiodarone and flecainide because of excessive sinus bradycardia. Two patients, with previously documented atrial flutter, experienced presyncopal episodes of atrial flutter with 1:1 atrioventricular (AV) conduction and wide QRS complex. No death occurred during the follow-up. In this series, quinidine proved to be unsuccessful in 46 patients and it was withdrawn in 6. We concluded that flecainide is efficient and well tolerated for long-term prevention of PAF in patients resistant to quinidine. The possibility of 1:1 AV conduction during atrial flutter may suggest the use of verapamil or beta blockers in combination with flecainide in patients with previously documented atrial flutter.

Results of electrical fulguration in arrhythmogenic right ventricular disease.

Eleven patients with sustained ventricular tachycardia (VT) refractory to antiarrhythmic drugs due to right ventricular disease shown by angiography underwent fulguration. Seven patients always had VT with the same morphology, and 4 had clinical VT with 2 or 3 different QRS waveforms. Five patients underwent a single fulguration and the other 6 underwent from 2 to 5 procedures; 2 to 14 shocks (mean 6) of 150 to 250 J were used. No serious complications occurred. At 31.5 +/- 9 months of follow-up, the arrhythmia was controlled in 8 patients, with continuation of previously ineffective antiarrhythmic drug therapy in 6 of 8. The number of VT episodes the year before and after fulguration was 0.5 +/- 0.7 vs 3.5 +/- 1.7 (p less than 0.001). There was no statistically significant difference between the success rate and the degree of prematurity of the onset of the local electrogram during VT: -36 +/- 31 ms for successes and -38 +/- 13 ms for failures. In 7 patients with monomorphic VT, there were 6 successes and 1 failure, and in 4 patients with several morphologies of VT, there were 2 successes and 2 failures (1 due to the appearance of a "new" VT). Thus, electrical fulguration of VT in patients with right ventricular disease is safe and most often effective, particularly in patients with monomorphic VT, when combined with antiarrhythmic drugs. In these patients, the usually recommended endocardial mapping criteria for the determination of the optimal fulguration site were not predictive of outcome. Further studies are necessary to better define the optimal site for fulguration.

Logic and empiricism in the selection of antiarrhythmic agents. The role of drug combinations.

Advances in investigative techniques of cardiac arrhythmias through invasive procedures (clinical electrophysiology) or through ambulatory electrocardiographic monitoring provide a better understanding of the mechanism responsible for these disturbances and a better assessment of therapeutic efficacy. Yet, it cannot be inferred that the selection of antiarrhythmic agents is orientated in all cases by logical reasoning. Too many factors are unknown, especially those regarding the spontaneous mechanism of initiation of clinical arrhythmias. Patient management very often remains mainly empirical. The problem becomes even more complex when dealing with arrhythmias resistant to single-agent therapy. Drug combinations are then used, often successfully, particularly those combining membrane-stabilising agents with amiodarone or beta-adrenergic blocking agents or combining amiodarone with verapamil. Explanations of the efficacy of these combinations at reduced doses become less certain, but it is more important to achieve efficacy than to understand its mechanism, which does not always amount to a simple increase in plasma drug levels. When attempting to determine the reasons behind the theoretically logical selection of an antiarrhythmic agent, it appears that, in spite of advances in electrophysiology and pharmacology, the logic of this selection owes more to chance than to reason. The problem becomes further complicated when drug combinations are to be used which, in clinical practice, are often the therapeutic solution in difficult cases. Advances made in recent years bring up the question of knowing whether or not logic is near to replacing empiricism.

[Prognostic factors for success in catheter ablation of the right Kent bundle: report of 27 patients]. / Factores pronóstico de éxito en la fulguración de los haces de Kent derechos: a propósito de una serie de 27 pacientes.

In 27 patients with atrial fibrillation and/or reciprocating tachycardia, ablation of right-sided Kent bundles (23 in the right posterior paraseptal region and four of the right free wall) was performed. The anterograde refractory period of the accessory pathways was 253 +/- 70 msec and the shortest R-R interval during atrial fibrillation 211 +/- 47 msec. Cumulative energies of 589 +/- 396 J per patient were used, with 3 +/- 2 shocks and 195 +/- 312 J per shock. Accessory pathway ablation was effective in 16/27 patients (59%) during an 11 +/- 8 months of follow-up (in 15/16 pre-excitation disappeared; in nine of them the anterograde and retrograde conductions were abolished and in the other six the anterograde and retrograde conductions were severely altered; ablation was partially ineffective in 1/16 patients who remained asymptomatic on medical treatment and without inducible reciprocal rhythm). Ablation was ineffective in 11/27 patients. Three hours after ablation a patient died from electromechanical dissociation; during ablation a 200 J shock cancelled preexcitation, not being possible to produce reciprocal rhythm. The emergency echocardiography only showed a minimum posterior pericardial effusion. Ablation was effective in 15/23 patients (65%) right posterior paraseptal. Overall success in 1989 (10/27 patients) was 70% (7/10 patients). The success in 1989 was 70% (6/8 patients) right posterior paraseptal. The shortest RP' interval (was 82 +/- 19 msec) during the reciprocal rhythm, where the ablation was performed, was 82 +/- 19 msec (74 +/- 17 msec with success and 99 +/- 19 msec with failure).(ABSTRACT TRUNCATED AT 250 WORDS)

[Mechanisms determining sudden death. A cooperative study of 69 cases recorded using the Holter method]. / Mise en évidence des mécanismes déterminants de la mort subite. Enquête coopérative portant sur 69 cas enregistrés par la méthode de Holter.

A cooperative study involving 23 centres enabled review of 69 cases of sudden death occurring less than one hour after onset of symptoms recorded by the Holter method and not related to recent, clinically documented myocardial infarction or to class IV cardiac failure. The 15 cases of asystole (22 p. cent) were observed in elderly patients (73.3 +/- 2.7 years) whose known ischaemic heart disease (12/15) was confirmed in 10 cases as the direct cause by the preceding acute ST changes. In 2 cases, death resulted from AV block presumed to be iatrogenic. The 13 episodes of torsades de point (19 p. cent) occurred mainly in younger women (58.8 +/- 6 years) without apparent cardiac disease (8 cases) and were provoked by a Group IA antiarrhythmic drug (7 cases) or by hypokalemia (3 cases). Apart from 1 case of congenital long QT syndrome, slowing of the sinus rhythm was observed (78.3 +/- 2.6 to 60.2 +/- 2.7 bpm, p less than 0.001) in the 3 hours preceding these episodes, and ventricular bigeminy with a long coupling interval was recorded in the lasts seconds before the torsades. The 41 (59 p. cent) cases of ventricular fibrillation (VF) were observed in men aged 64.9 +/- 2 years with coronary artery disease (39/41). However signs of acute ischaemia were only found in 5 cases. The VF was primary in 8 cases and secondary to ventricular tachycardia (VT in 33 cases). An acceleration of the cardiac rhythm (83.3 +/- 3.4 to 90 +/- 4.1 bpm, p less than 0.01) was recorded in the hour preceding VF and other arrhythmias were common: atrial tachycardia (4 cases), atrial extrasystoles (4 cases), a new type of ventricular extrasystoles (VES). The VF and VT were preceded by a long cycle in 17 cases. The first complex was different from previous VES in 10 cases and identical to the previous VES in 16 cases; in 4 cases this feature could not be identified and in 11 cases there were no premonitory VES. The coupling interval of the initial VES was shorter than that of the most premature preceding VES (368 +/- 13 ms vs 442 +/- 19 ms, p less than 0.001), especially in primary VF (335 +/- 9 ms, N = 8) compared to polymorphic VT (360 +/- 12 ms, N = 11) or monomorphic VT (384 +/- 18 ms N = 22).(ABSTRACT TRUNCATED AT 250 WORDS)

[Life expectancy after a first attack of sustained monomorphic ventricular tachycardia. Apropos of 295 patients with a follow-up of more than 5 years]. / Espérance de vie après une première crise de tachycardie ventriculaire monomorphe soutenue. A propos de 295 patients suivis plus de 5 ans.

Analysis of actuarial cardiac mortality of 295 patients after a first attack of sustained monomorphic ventricular tachycardia followed up for an average of 5.1 years showed that: the aetiology was the main prognostic factor. Patients with a normal left ventricle had a zero 5 year mortality rate (normal heart) or 3% (arrhythmogenic right ventricular dysplasia) compared with 24% in patients with cardiomyopathy and 40% with myocardial infarction: p less than 0.01. Similar results were obtained if sudden death was considered; in patients with left-ventricular disease, the role of pump function assessed by the ejection fraction was essential: the 5 year mortality was 14.5% (cardiomyopathy) and 30% (myocardial infarction) if this was greater than 0.3 compared to 43% and 51% respectively when less than 0.3 (p less than 0.01); the heart rate of spontaneous ventricular tachycardia and that of tachycardia induced during endocavitary investigation had no influence on the mortality. However, the mortality following a first tachycardia with syncope was higher than that following a well tolerated tachycardia (p less than 0.5 if the ejection fraction less than or equal to 0.3 and p less than 0.001 if greater than 0.3).(ABSTRACT TRUNCATED AT 250 WORDS)

[Value of searching ventricular late potentials in patients recovering from ventricular fibrillation]. / Intérêt de la recherche des potentiels tardifs ventriculaires chez les patients réanimés de fibrillation ventriculaire.

The prognostic value of ventricular late potentials (VLP) was studied in 38 survivors of ventricular fibrillation (VF) resuscitated after cardiac arrest. Thirty-seven patients had coronary artery disease, 24 within one month of myocardial infarction, and one patient had valvular heart disease. There were 7 deaths within 2 years, including 5 sudden deaths, the average follow-up in the remaining patients being 46 +/- 30 months. Bad prognostic factors included low left ventricular ejection fraction, anterior myocardial infarction, VF occurring after the first 24 hours of myocardial infarction and the presence of VLP. The 2 year mortality rate was 35% in patients with VLP compared with only 5% when they were absent (p < 0.05). The subgroup with the highest risk of death was that of anterior myocardial infarcts with VLP (45% 2 year mortality). The clinical circumstances surrounding VF were important; patients with clinical and electrical signs of ischaemia at the time of VF tended to have a better prognosis than the others, especially in the absence of VLP: in this subgroup of 12 "ischaemic" VFs without VLP the mortality at 2 years was nil, whereas the other 26 patients had a 27% death rate (0.05 < p < 0.10). Programmed ventricular stimulation was only carried out in 14 cases: it showed that the long-term mortality was very high (60%) in patients with VLP and inducible ventricular tachycardia (VT). Therefore, the implantation of an automatic defibrillator device would seem to be justified in patients resuscitated from VF who have both VLP and inducible VT, but of no value in cases of "ischaemic" VF without VLP.

[Value of flecainide in supraventricular arrhythmias]. / Intérêt de la flécaïnide dans les troubles du rythme suppraventriculaire.

Flecainide acetate (Flecaine) is a new antiarrhythmic which has recently become available; its efficacity in treatment of ventricular rhythm disorders has been amply demonstrated. In this study we have evaluated its efficacity per os in treatment of auricular rhythm disorders refractory to the usual therapies, and its effects on the accessory routes of atrioventricular conduction. The results are very promising and better than those obtained with amiodarone in auricular disorders. They show that flecainide is a drug of importance among therapeutic agents used in treatment of auricular arrhythmia, and its action on Kent's bundle makes it a drug of choice in management of Wolff-Parkinson-White syndrome, especially as it seems equally efficacious in its action on the accessory routes with a short refractory period. Most of our patients did not present organic cardiopathy and the side-effects were generally benign. A non-negligible number of cases of paroxysmal hypertension were noted, in disagreement with literature data, and this point needs to be clarified by further study.

[A case of severe catecholaminergic bitachycardia]. / Un cas de bitachycardie catécholergique sévère.

The authors report the electrophysiological study of severe catecholaminergic double tachycardia in a young athletic subject with an apparently healthy heart. The literature is reviewed and the mechanisms of double tachycardia are discussed, together with the role of the sympathetic nervous system and the therapeutic implications.

[Idiopathic dilatation of the heart atrium with complete auricular paralysis]. / Dilatation idiopathique des oreillettes avec paralysie auriculaire complète.

The authors report the case of a patient with idiopathic dilatation of the auricles and complete atrial paralysis associated with absence of excitability of the atrial muscle. Repeated echocardiograms over a period of three months demonstrated dilatation of the auricles and ventricles with the development of mitral and tricuspid incompetence. The role played by the junctional bradycardia in the ventricular dilatation is discussed and the patient was explored haemodynamically with varying rates of ventricular pacing. In view of the improvement in the haemodynamic parameters, a cardiac pacemaker was inserted. After a follow-up of one year, the ventricular chambers have returned to normal and the mitral and tricuspid incompetence has regressed, while the atrial muscle continues to dilate. The patient is currently asymptomatic with no medical treatment.

[Efficacy of high doses of molar lactate by the venous route in flecainide poisoning]. / Efficacité de fortes doses de lactate molaire par voie veineuse lors des intoxications au flécaïnide.

Three cases of intoxication by flecainide acetate were characterized by cardiovascular collapse with widening of the QRS complex at electrocardiography. In two of these patients, impairment of liver or renal function probably played a facilitating role. Infusion of molar sodium lactate in high doses resulted in rapid and durable clinical and electrocardiographic improvement. This effect of molar sodium lactate may tentatively be attributed to either displacement of flecainide from its tissue receptor sites, or to a decrease in the effect of flecainide by alteration of its action on the fast sodium channel, or to the beneficial effects of vascular filling.

Hypertension in pregnancy: evaluation of two beta blockers atenolol and labetalol.

There is a major controversy over the relative value of anti-hypertensive drugs in hypertension in pregnancy. Our purpose was to study two different beta-adrenolytic drugs, atenolol, a cardioselective beta blocker, and labetalol, an alpha-beta blocker. Fifty-six hypertensive (BP greater than 140/90 mmHg) pregnant women were treated either with atenolol or labetalol. The patients were divided into two subgroups for which there were no statistical differences with regard to age, number of previous pregnancies, initial level of blood pressure and uricemia, proteinuric pre-eclampsia, beginning of therapeutic trial and delivery. The average daily dosage was 144.6 +/- 47.8 mg day-1 with atenolol and 614 +/- 47.8 mg day-1 with labetalol. This study shows: the same anti-hypertensive effect of the two drugs with control of blood pressure in 82% of the cases; a birth-weight significantly higher with labetalol (3280 +/- 555 g) than with atenolol (2750 +/- 630 g) (P less than 0.001); two still-births with atenolol; no adverse effects of the drugs during pregnancy and the neo-natal period; the trans-placental passage of atenolol and labetalol as shown by plasma dosages in the mothers and the new-born. It is concluded that atenolol and labetalol are safe and they are usually effective in the control of the hypertension complicating pregnancy. But labetalol appears to be better able to prevent the appearance of fetal growth retardation.

Long-term follow-up after sustained monomorphic ventricular tachycardia: Causes, pump failure, and empiric antiarrhythmic therapy that modify survival.

We analyzed the actuarial cardiac mortality rate of 295 consecutive patients with sustained monomorphic ventricular tachycardia who were referred to us between 1978 and 1988. Patients were divided into four groups: group I of 156 patients with coronary disease, group II of 55 patients with nonischemic left ventricular disease, group III of 65 patients with right ventricular disease, and group IV of 19 patients without detectable heart disease. Patients were treated empirically according to a prospective schema: (1) class I antiarrhythmic drugs, (2) in case of recurrence of ventricular tachycardia: amiodarone or beta-blockers, (3) in case of recurrence of ventricular tachycardia: drug combinations or surgery. The mean follow-up duration was 61 +/- 40 months after the first occurrence of ventricular tachycardia, and the clinical outcome was known in 67.5% of patients at 5 years. The actuarial mortality rates were considerably higher in groups I and II compared with those in groups III and IV (p less than 0.01). The mortality rate was slightly higher in group I than in group II (p less than 0.05). In groups I and II, actuarial mortality rate were much higher when left ventricular ejection fraction was less than 0.30 (p less than 0.01). Comparisons between treatments showed no difference in actuarial mortality rates in patients with ventricular tachycardia and left ventricular ejection fraction greater than 0.30.(ABSTRACT TRUNCATED AT 250 WORDS)