Electromechanical window negativity in genotyped long-QT syndrome patients: relation to arrhythmia risk

Aim Prolonged and dispersed left-ventricular (LV) contraction is present in patients with long-QT syndrome (LQTS). Electrical and mechanical abnormalities appear most pronounced in symptomatic individuals. We focus on the 'electromechanical window' (EMW; duration of LV-mechanical systole minus QT interval) in patients with genotyped LQTS. Profound EMW negativity heralds torsades de pointes in animal models of drug-induced LQTS. Methods and results We included 244 LQTS patients from three centres, of whom 97 had experienced arrhythmic events. Seventy-six matched healthy individuals served as controls. QT interval was subtracted from the duration of Q-onset to aortic-valve closure (QAoC) midline assessed non-invasively by continuous-wave echocardiography, measured in the same beat. Electromechanical window was positive in controls but negative in LQTS patients (22 +/- 19 vs. -43 +/- 46 ms; P <0.0001), being even more negative in symptomatic than event-free patients (-67 +/- 42 vs. -27 +/- 41 ms; P, 0.0001). QT, QTc, and QAoC were longer in LQTS subjects (451 +/- 57, 465 +/- 50, and 408 +/- 37 ms, P <0.0001). Electromechanical window was a better discriminator of patients with previous arrhythmic events than resting QTc (AUC 0.77 (95% CI, 0.71-0.83) and 0.71 (95% CI, 0.65-0.78); P = 0.03). In multivariate analysis, EMW predicted arrhythmic events independently of QTc (odds ratio 1.25; 95% CI, 1.11-1.40; P = 0.001). Adding EMW to QTc for risk assessment led to a net reclassification improvement of 13.3% (P = 0.03). No EMW differences were found between the three major LQTS genotypes. Conclusions Patients with genotype-positive LQTS express EMW negativity, which is most pronounced in patients with documented arrhythmic events.