[Non-channel drugs to prevent atrial fibrillation]. / A pitvarfibrilláció nem ioncsatornára ható gyógyszeres kezelése.

Atrial fibrillation is the most prevalent sustained cardiac arrhythmia. To terminate or prevent atrial fibrillation, conventional "channel-blocking antiarrhythmics" are generally administered, which directly inhibit current flows through transmembrane sodium, calcium and/or potassium channels that give rise to the atrial action potential. However, prospective, randomized clinical trials have demonstrated that cardiomyocyte ion channel blocking antiarrhythmic drugs have limited long-term-efficacy for preventing recurrences of atrial fibrillation, their safety is far from ideal (because of the high incidence of proarrhythmic and extracardiac side-effects), and do not reduce mortality. Researchers during the last 10 years have revealed that the pathogenetic basis of the recurrence, persistence or permanence of atrial fibrillation is electrical and structural remodelling established by profound alterations in the electrophysiological, contractile and (ultra)structural properties of the myocardium (atrial remodelling). Accordingly, recent interest has shifted from ion channel blockers to the development of drugs that target underlying arrhythmogenic substrates by interference with receptors and specific signal transduction pathways involved in electrical and structural remodelling (non-channel drugs). They include antifibrotic angiotensin-converting enzyme inhibitors, angiotensin II AT1 receptor and aldosterone antagonists, beta-adrenergic blockers, anti-inflammatory statins and glucocorticoids, and a series of new atrioselective antifibrillatory agents that are currently undergoing clinical trials.

[Proarrhythmic (torsadogenic) effects of QT-prolonging non-antiarrhythmic drugs]. / Az EKG QT-idoszakaszát megnyújtó nem antiarrhythmiás gyógyszerek ritmuszavarkelto (torsadogen) hatása.

The authors review the rapidly expanding knowledge relating to the arrhythmogenic (torsadogenic) effects of non-antiarrhythmic drugs that lengthen ventricular repolarization (i.e. the duration of electrocardiographic QT interval). After outlining the ECG characteristics and electrophysiological mechanism of drug-induced long-QT syndrome and torsades de pointes ventricular tachycardia, they discuss the concept of repolarization reserve and its role in arrhythmogenesis. Information is provided on the cardiac ion channel background of the proarrhythmic action of QT-prolonging non-antiarrhythmic drugs. The authors present pharmacoepidemiological data on the clinical importance and incidence of this peculiar adverse drug reaction that can in certain cases cause sudden arrhythmic death. They draw attention to the predisposing factors of torsades de pointes ventricular tachycardia, and list those groups of drugs and individual agents that have QT-lengthening and torsadogenic side-effects.

[Torsades de pointes ventricular tachycardia induced by intravenous amiodarone]. / Intravénás amiodaron által elóidézett torsades de pointes kamrai tachycardia.

The authors report on the case history of a 61 year old woman with hyperthyroidism induced atrial fibrillation, tachycardiomyopathy and congestive heart failure, in whom life threatening ventricular proarrhythmia (torsades de pointes) developed in response to intravenous amiodarone. The patient in a septic state was resuscitated because of ventricular fibrillation. The atrial fibrillation complicated by a high ventricular frequency was slowed down with intravenous amiodarone; additionally, the iodine-containing antiarrhythmic drug was expected to counter thyrotoxicosis. In response to amiodarone (2 x 300 mg), the sinus rhythm was restored, but the excessive post-cardioversion bradycardia led to the development of extreme QT interval prolongation and torsades de pointes ventricular tachycardias that often degenerated into ventricular fibrillation. In connection with this case, the authors survey those electropharmacological and pathophysiological factors which may have played a role in the emergence of ventricular proarrhythmia based on a lengthening of repolarization through the exhaustion of the repolarization reserve.

[Clinical proarrhythmias induced by anti-arrhythmic drugs, non-cardiovascular agents and implantable cardioverter-defibrillators]. / Antiarrhythmiás és nem-szívérrendszeri gyógyszerek, valamint beültethetó cardioverter-defibrillátorok által elóidézett klinikai proarrhythmiák.

The authors survey the electrophysiological mechanisms and clinical spectrum of the aggravation of cardiac arrhythmias provoked by antiarrhythmic drugs, non-cardiovascular agents and implantable cardioverter-defibrillators. The main aspects of the recognition, the differential diagnostics and the therapy are discussed. It is demonstrated that prevention of drug-induced arrhythmogenesis necessitates a fundamental understanding of the risk factors of proarrhythmias and of the clinical pharmacological properties of the drugs that are intended to be used, including proarrhythmic drug interactions. A systematic account is presented of those drugs prescribed in non-arrhythmic diseases which may lead to out-of-hospital cardiac arrest. The proarrhythmias that may be observed in recipients of implantable cardioverter-defibrillators are discussed, as are the undesirable interactions between these devices and antiarrhythmic drugs in such patients.

[History of atrial fibrillation]. / A pitvarfibrilláció története.

The authors review the history of atrial fibrillation, the most frequent clinically observed cardiac arrhythmia. A French "clinicopathologist", Jean Baptist de Sénac (1693-1770), was the first who assumed a correlation between "rebellious palpitation" and a stenosis of the mitral valve. From an analysis of simultaneously recorded arterial and venous pressure curves, the Scottish Sir James Mackenzie (1853-1925) demonstrated that a praesystolic a wave can not be seen on the jugular phlebogram during "pulsus irregularis perpetuus". The first human ECG depicting atrial fibrillation was published by Willem Einthoven (1860-1927) in 1906. The proof of a direct connection between absolute arrhythmia and auricular fibrillation was established by two Viennese physicians, Rothberger and Winterberg. The major discoveries relating to the pathomechanism and the clinical features of atrial fibrillation in the 20th century stemmed from the scientific activities of Karel Frederik Wenckebach, Sir Thomas Lewis, Gordon Moe and Maurits Allessie.