Investigation of mechanisms and non-pharmacological therapy of cardiac arrhythmias

Learning of mechanisms of arrhythmias may contribute substantially to the development of effective pharmacological and non-pharmacological therapeutic methods. Clinical relevance of endothelin-1 (ET-1), a strong vasoconstrictor and arrhythmogenic endogenous substrate, is not clarified yet. In our experimental studies, performed in the in situ canine heart, electrophysiological effects and the role in the pathomechanism of malignant ventricular tachyarrhythmias of endogenous and exogenous ET-1 was investigated. It has been proven in the in vivo ischaemia-reperfusion canine heart model, that during reperfusion ET-1 and big-ET levels increase in the coronary sinus, however there was no correlation between endothelin levels and electrophysiological changes. ET A-receptor antagonist darusentan does not prevent electrophysiological changes and development of ventricular tachyarrhythmias during ischaemia and reperfusion. On the contrary, during ischaemia endogenous ET-1 tends to show balancing effect. It has been proven that administration of high dose intracoronary ET-1 bolus has dual, ischaemic and direct, electrophysiological effect. It has been shown for the first time, that ET-1 causes monophasic action potential (MAP) and T-wave alternant. Our clinical study leads to the conclusion that previous atrial fibrillation, absence of preoperative beta-blocker treatment and combined heart surgery are strong predictors of atrial fibrillation following open heart surgery. The basis of new nonpharmacological therapies is the learning of pathomechanisms of arrhythmias and in some cases heart failure, which is an arrhythmogenic substrate. In our experimental study reliable MAP measurements, suitable for investigation of arrhythmogenesis, were performed for the first time using fractally coated ablation catheters during spontaneous rate and during stimulations. It has been proven that radiofrequency ablation affects significantly MAP parameters. In Hungary, we were the first to apply effectively biatrial pacemaker and biatrial cardioverter defibrillator for the prevention of paroxysmal atrial fibrillation. In the majority of patients frequency of paroxysmal atrial fibrillation decreased significantly due to biatrial stimulation or combined pharmacological and resynchronisation therapy. Parasymphathetic cardiac neurostimulation is a promising new non-pharmacological treatment option in certain types of arrhythmias. In our clinical study we were able to stimulate cardiac parasympathetic nerves innervating atrioventricular node achieving ventricular rate control during atrial tachyarrhythmias with chronically implanted coronary sinus lead. In our study biventricular pacemakers and cardioverter defibrillators were applied successfully in the treatment of drug refractory congestive heart failure combined with inter- and/or intraventricular conduction disturbances. AV sequential left sided chronic pacing using a single lead located in the coronary sinus has not been previously reported. Left sided DDD pacing was effective chronically in the improvement of the functional stage of patient suffering from congestive heart disease combined with left bundle branch block and binodal disease. Parallel with the investigation of pathomechanism of life-threatening ventricular tachyarrhythmias and the most common, clinically relevant atrial fibrillation due to recent technical development, we were able to support nonpharmacological therapeutic modalities, gaining popularity in clinical management, with novel observations.