New electrocardiographic risk factor for serious cardiac events in Andersen-Tawil syndrome

Andersen-Tawil syndrome (ATS, LQTS7) is an ultra-rare channelopathy caused by pathogenic variants in KCNJ2. The disease manifests with a triad of symptoms: ventricular arrhythmia and a prominent U wave in the ECG, dysmorphic features and periodic paralysis. Due to the small number of studies, the assessment of the risk of sudden cardiac arrest (SCA) is very difficult. Until recently, ATS was considered a relatively benign syndrome, but there are still reports of a more dangerous nature of the disease. So far, it has been shown that the risk factors for serious cardiac events are syncope and stable sVT.

Objectives of the study: The main objective of the study was to find electrocardiographic risk factors for serious cardiac events in ATS defined as SCA, adequate ICD intervention, syncope. Another objective was to assess the course of the disease and to identify characteristic features that may be helpful in the diagnosis of ATS.

The study included 44 patients with confirmed pathogenic variant in KCNJ2 (73% women, mean age 36.2 +/- 15.6). Interview, physical examination, ECG, 24h-Holter ECG, exercise test were assessed. The highest risk group (n = 5; 11%) with a history of SCA or adequate ICD intervention and the high risk group (n = 18; 41%) with a history of SCA or adequate ICD intervention or syncope were distinguished. The parameters were compared with the results of the remaining patients who constituted the control groups (n = 39, n = 26, respectively). Cut-off points were selected for measurable parameters.

In the highest risk group, predictors of SCA or appropriate ICD interventions were QTUc > 750ms (p = 0.007), %VEBs > 30% (p < 0.001), and max VEBs > 40k/24h (p < 0.001), occurrence of sVT (p = 0.003), and history of sycope (p = 0.008). Predictors of events in the high risk group were QTUc > 680ms (p = 0.011), %VEBs > 6% (p < 0.001), max VEBs > 4.8k/24h (p < 0.001), and occurrence of sVT (p = 0.022), bidirectional VT (p = 0.046), ventricular couplets (p = 0.003), and U wave height (p = 0.043). A higher risk of cardiac symptoms was found in women (p = 0.0019). In all patients (n = 44, 100%), QTUc > 620ms was found and in the majority (n = 44; 100%), U wave height > 1.5mm (n = 29, 67%).

ATS is not a benign channelopathy. In the study group, SCA or appropriate ICD interventions occurred in 11% of patients. The study confirmed previously known risk factors: history of syncope and the occurrence of sVT and detected new electrocardiographic prognostic indicators: QTUc > 750ms, %VEBs > 30%, and maximum number of VEBs > 40 thousand/24h. In addition, it was found that new parameters assessed in ECG may be useful in ATS diagnostics: QTUc > 620 ms and U wave height > 1.5 mm.