Primäre kardiale Ionenkanalerkrankungen als Ursache des plötzlichen Herztodes

In Deutschland sterben ca. 120000 Menschen pro Jahr (USA: 300000-400000/Jahr) am plötzlichen Herztod, der hauptsächlich durch strukturelle Herzerkrankungen wie der koronaren Herzkrankheit oder Kardiomyopathien hervorgerufen wird. Ungefähr 1% dieser Fälle sind auf primäre kardiale Ionenkanalerkrankungen (primary arrhythmogenic disorders) zurückzuführen; dabei handelt es sich fast ausschliesslich um junge, meist gesunde Patienten ohne Zeichen einer strukturellen Herzerkrankung. Diese angeborenen kardialen Ionenkanalerkrankungen haben mutationsbedingte Dysregulationen von verschiedenen Ionenkanälen, Ionenkanal-interagierenden (Hilfs)-Proteinen oder zytosolischen Proteinen zur Folge. Mutationsbedingte Funktionsstörungen, die zu Veränderungen verschiedener Kalium- (IKs, IKr, IK1), Natrium- (INa), Kalzium-Ionenströme (ICa) bzw. der intrazellulären Kalzium-Homöostase führen, werden ursächlich für diese angeborenen Ionenkanalerkrankungen wie das Long-QT-Syndrom, das Short-QT-Syndrom, das Brugada-Syndrom und die katecholaminerge polymorphe ventrikuläre Tachykardie verantwortlich gemacht. Dieser Übersichtsartikel stellt eine Zusammenfassung von Pathophysiologie, Klinik, Diagnostik und Therapie dieser Syndrome dar. Das klinische Erscheinungsbild reicht von asymptomatischen Verläufen bis hin zum plötzlichen Herztod. Die ICD-Implantation nimmt insbesondere bei Hochrisikopatienten den größten therapeutischen Stellenwert ein. Ein besseres molekularbiologisches Grundlagenverständnis über diese kardialen Ionenkanalerkrankungen verspricht neue Wege der Diagnostik (genspezifische Risikostratifizierung) und der genspezifischen Therapie.

Summary

Sudden cardiac death (SCD) has an incidence of around 120000 individuals per year in Germany (US: 300000-400000/a). It is predominantly caused by structural heart diseases such as coronary artery disease or cardiomyopathies. About 1% of SCD is caused by primary arrhythmogenic disorders especially in young patients without structural heart disease. These inherited cardiac channelopathies are genetic disorders based on DNA mutations of different ion-channels and ion-channel interacting-proteins. Mutations in these genes encoding cardiac ion-channels, auxiliary (modulating) proteins or cytosolic-intercellular proteins, which are important for different potassium (IKs, IKr, IK1), sodium (INa) and calcium currents (ICa) or cytosolic calcium homeostasis, have been associated with different primary electrical diseases such as Long-QT-syndrome, Short-QT-syndrome, Brugada-syndrome and catecholaminergic polymorphic ventricular tachycardia. This article reviews the pathophysiological mechanisms and clinical features as well as diagnostic and therapeutic features of these syndromes. Their clinical manifestations range from an asymptomatic course to sudden cardiac death. Therapies include pharmacological tools and/or implantation of a cardioverter-defibrillator in high-risk patients. Improved understanding of the basic biology of these cardiac ion-channel diseases holds the promise of identifying new molecular targets for better diagnosis such as gene-risk stratification and specific treatment of these primary arrhythmogenic disorders.

Schlüsselwörter

plötzlicher Herztod - primäre kardiale Ionalerkrankungen

Key words

sudden cardiac death - primary cardiac ion-channel diseases

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