Short QT syndrome.
The short QT syndrome constitutes a new clinical entity that is associated with a high incidence of sudden cardiac death, syncope, and/or atrial fibrillation even in young patients and newborns. Patients with this congenital electrical abnormality are characterized by rate-corrected QT intervals<320 ms. Missense mutations in KCNH2 (HERG) linked to a gain-of-function of the rapidly activating delayed-rectifier current I(Kr) have been identified in the first two reported families with familial sudden cardiac death. Recently, two further gain-of-function mutations in the KCNQ1 gene encoding the alpha-subunit of the KvLQT1 (I(Ks)) channel and in the KCNJ2 gene encoding the strong inwardly rectifying channel protein Kir2.1 confirmed a genetically heterogeneous disease. The possible substrate for the development of ventricular tachyarrhythmias may be a significant transmural dispersion of the repolarisation due to a heterogeneous abbreviation of the action potential duration. The implantable cardioverter defibrillator is the therapy of choice in patients with syncope and a positive family history of sudden cardiac death. However, ICD therapy in patients with a short QT syndrome has an increased risk for inappropriate shock therapies due to possible T wave oversensing. The impact of sotalol, ibutilide, flecainide, and quinidine on QT prolongation has been evaluated, but only quinidine effectively suppressed gain-of-function in I(Kr) with prolongation of the QT interval. In patients with a mutation in HERG, it rendered ventricular tachycardias/ventricular fibrillation non-inducible and restored the QT interval/heart rate relationship towards a normal range. It may serve as an adjunct to ICD therapy or as a possible alternative treatment, especially for children and newborns.
Schimpf
Rainer
R
1st Department of Medicine-Cardiology, University Hospital Mannheim, Theodor-Kutzer-Ufer 1-3, D-68167 Mannheim, Germany. rainer.schimpf@med.ma.uni-heidelberg.de
Wolpert
Christian
C
Gaita
Fiorenzo
F
Giustetto
Carla
C
Borggrefe
Martin
M
D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use; D016757:Death, Sudden, Cardiac; D017147:Defibrillators, Implantable; D003937:Diagnosis, Differential; D004554:Electric Countershock; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics*; D006801:Humans; D020125:Mutation, Missense; D014693:Ventricular Fibrillation / Q000175:diagnosis / Q000235:genetics* / Q000628:therapy
D000889:Anti-Arrhythmia Agents; D051638:Ether-A-Go-Go Potassium Channels; C092509:KCNH6 protein, human