The Relationship between T-Wave Alternans and Adverse Cardiac Events in Patients with Congenital Long QT Syndrome: A Systematic Review and Meta-Analysis

Background: T-wave alternans (TWA) is a risk factor of ventricular arrhythmias or sudden cardiac death (SCD) in patients with ischemic cardiomyopathy. Nevertheless, the relationship between TWA and adverse cardiac events (ACE) in patients with congenital long QT syndrome (LQT) remains controversial. Methods: A systematic electronic search of PubMed, Embase and the Cochrane Library was conducted from database inception dates to 28 April 2021 and assessed the relationship between TWA and ACE in patients with LQTS. Sub-group analysis evaluated the association between microvolt TWA (MTWA) and ACE in different monitoring models and ECG-lead numbers. Results: A pooled analysis of seven studies of 625 patients with LQTS showed that TWA was significantly associated with ACE (OR 3.16, 95%CI 1.86-5.37, P < 0.001). Advanced analysis showed that macro-scopic TWA was significantly related to ACE (OR 6.01, 95%CI 2.96-12.21, P < 0.001), while MTWA did not (OR 0.92, 95%CI 0.37-2.30, P = 0.85). Sub-group analysis showed that MTWA recorded in 24 h continuous ECG (OR 6.79, 95%CI 0.80-57.75, P = 0.08) might have a stronger association with ACE than recorded in stress ECG (OR 0.28, 95%CI 0.07-1.10, P = 0.07). No difference was observed between MTWA measured in multi-lead ECG and limited ECG leads (P = 0.15). Conclusions: Macroscopic TWA was significantly related to ACE in patients with LQTS. In terms of MTWA, MTWA recorded in 24 h continuous ECG might have a stronger association with ACE than stress ECG, but still deserves further evaluation.