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

• Published in: European heart journal Vol. 36; no. 3; pp. 179 - 186
• Main Authors: ter Bekke, Rachel M.A., Haugaa, Kristina H., van den Wijngaard, Arthur, Bos, J. Martijn, Ackerman, Michael J., Edvardsen, Thor, Volders, Paul G.A.
• Format: Journal Article
• Language: English
• Published: England 14.01.2015
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Adult; Analysis of Variance; Anti-Arrhythmia Agents - therapeutic use; Arrhythmias, Cardiac - genetics; Case-Control Studies; Death, Sudden, Cardiac - prevention & control; Electrocardiography; ERG1 Potassium Channel; Ether-A-Go-Go Potassium Channels - genetics; Female; Genotype; Heterozygote; Humans; Ion Channels - genetics; Ion Channels - physiology; KCNQ1 Potassium Channel - genetics; Long QT Syndrome - drug therapy; Long QT Syndrome - genetics; Long QT Syndrome - physiopathology; Male; Mutation - genetics; NAV1.5 Voltage-Gated Sodium Channel - genetics; Potassium Channels, Voltage-Gated - genetics; Risk Factors; Ultrasonography, Doppler; Ion channels; Long-QT syndrome; Echocardiography; Arrhythmia; Sudden death
• ISSN: 0195-668X; 1522-9645; 1522-9645
• DOI: 10.1093/eurheartj/ehu370

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. 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. Patients with genotype-positive LQTS express EMW negativity, which is most pronounced in patients with documented arrhythmic events.