[Heart hypertrophy and heart failure--experimental findings for arrhythmogenesis].
One major cause of sudden cardiac death in heart failure is the occurrence of life-threatening polymorphic ventricular tachycardia. Especially in the early stages of heart failure half of the deaths are sudden and unexpected. The majority of these are caused by ventricular tachyarrhythmias. Whereas reentry plays a major role in patients after myocardial infarction, triggered activity is responsible for the occurrence of arrhythmic events in non-ischemic heart failure. Action potential prolongation serves as the electrophysiological basis for the formation of triggered activity and the underlying early afterdepolarizations. It has been demonstrated in heart failure and in cardiac hypertrophy that this results from a reduction in outward repolarizing ion currents, especially due to downregulation of potassium channels. The underlying substrate for the maintenance of arrhythmias in chronic heart failure in experimental models and in humans is an increase in dispersion of repolarization. It opens the floodgate to the occurrence of potentially life-threatening polymorphic ventricular arrhythmias and leads to their maintenance. Thus chronic heart failure leads to a reduced repolarization reserve, i.e. a patient-specific response to risk factors that influence repolarization. Additional risk factors in patients with heart failure are hypokalemia (diuretic therapy), bradycardia (AV block) or concomitant therapy with repolarization prolonging drugs (antiarrhythmic drugs, antibiotics etc.) that may add further stress on the repolarization process and set the stage for the occurrence of life-threatening arrhythmias. One promising therapeutic approach to suppress arrhythmias in chronic heart failure may be a selective blocking of the Na+/Ca2+ exchanger. Experimental data have recently demonstrated a reduction of action potential duration, and dispersion of repolarization as well as suppression of early afterdepolarizations and torsade de pointes in an isolated intact heart model of chronic heart failure in a proarrhythmic milieu due to block of the Na+/Ca2+ exchanger.
Milberg
P
P
Medizinische Klinik und Poliklinik C, Kardiologie und Angiologie, Universitätsklinikum, Münster.
Pott
C
C
Eckardt
L
L
Breithardt
G
G
D000200:Action Potentials; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000401:mortality / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000150:complications* / Q000503:physiopathology; D016757:Death, Sudden, Cardiac / Q000453:epidemiology / Q000209:etiology; D006333:Heart Failure / Q000150:complications* / Q000503:physiopathology; D006801:Humans; D012307:Risk Factors; D019831:Sodium-Calcium Exchanger / Q000037:antagonists & inhibitors / Q000378:metabolism; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D016171:Torsades de Pointes / Q000209:etiology / Q000401:mortality / Q000503:physiopathology
D019831:Sodium-Calcium Exchanger; D002118:Calcium