Abstract 2700: KCNJ2-Specific ECG Abnormalities in Type 1 Andersen-Tawil Syndrome: The Enlarged U Wave, Prolonged QU Interval and Left Ventricular Arrhythmias
Type 1 Andersen-Tawil syndrome (ATS1) is a channelopathy caused by mutations in the KCNJ2-encoded Kir2.1 potassium channel and is clinically characterized by periodic paralysis, dysmorphic features and ventricular arrhythmias. Previously, we identified the gene-specific TU morphology changes in ATS1. Here, we hypothesized that ventricular arrhythmia in ATS1 may also have signature ECG features.
Methods ECG/Holter recordings were retrieved from an ATS1 database with 100 KCNJ2 mutation carriers for ventricular arrhythmias. TU morphologies, quantitative repolarization parameters and ventricular arrhythmias were analyzed.
As observed previously, an enlarged U wave was present in 73%, with an average normal QTc interval of 439±28 ms. QUc was markedly prolonged (ATS1 665±48 ms vs. normal control 600±40 ms, p<0.0001).
Ventricular arrhythmia was present in 44 of 100 KCNJ2 mutation carriers (25±15 years, 31 female). Individuals with ventricular arrhythmia had bigeminy (80%), non-sustained polymorphic VT (55%, 141±19 bpm), bi-directional VT (32%,131±7 bpm) and three patients had documented TdP (230±18 bpm).
Most ventricular ectopies occurred on the U wave (R-R’ 481±54 ms).
Most arrhythmias originated from left ventricle (98%), with 16% in the patterns of right bundle branch block (RBBB) and left anterior fascicular block (LAFB), 25% in RBBB and left posterior fascicular block (LPFB), and 52% alternated between RBBB+LAFB and RBBB+LPFB patterns. Left septal fascicular block (LSFB) pattern was seen in 48% (21/44) of ATS1 patients and was mostly associated with LAFB in (19/21).
The VT morphology and duration varied from beat to beat (4±3 morphologies, QRSD 151±17 ms). The last VT cycle was often the shortest (first R’-R’ 479±86 ms vs. last R’-R’ 432±67 ms, p<0.01).
Conclusions: ATS1-causing mutations in KCNJ2 are associated with specific ECG abnormalities including an enlarged U wave, marked QU prolongation and left ventricular arrhythmias. The latter is predominantly in females. The polymorphic and bidirectional VTs are mostly low rate tachycardia in patients with ATS1.