Temporal variability of electromechanical-window negativity in patients with inherited long-QT syndrome or drug-induced QT prolongation: relation to torsades de pointes

Abstract Background Electromechanical window (EMW) negativity is a novel parameter that identifies long-QT syndrome (LQTS) patients at increased arrhythmia risk. Whether the EMW remains stable or alters, especially close to arrhythmic events, is unknown. Purpose To study temporal variability of the EMW in controls and in patients with LQTS or drug-induced QT prolongation (di-QTprol), in relation to the timing of torsades de pointes (TdP) or ventricular fibrillation (VF). Methods In a retrospective cohort study with 5 participating centers, we assessed the EMW (ms) at 2 or 3 timepoints (if applicable, one of them close to TdP/VF) from cw-Doppler echocardiography in the apical long-axis view and concomitant ECG. EMW was calculated by subtracting the QT time from the aortic-valve closure time measured from QRS onset (surrogate of mechanical systole). Data are shown as mean±SD or median (25th to 75th percentile). Results Forty patients (75% female, 43±18 years old) were included: 8 controls, 27 LQTS (10 symptomatic: 9 TdP, 1 VF), and 5 di-QTprol (all TdP). LQTS genotypes were LQT1 (n=11), LQT2 (n=6), LQT3 (n=7), LQT7 (n=2), and genotype-negative (n=1). Overall, 67% of LQTS patients and 20% of di-QTprol were treated with β-blockers. Baseline QTc was 409±32 ms in controls, 444±32 ms in asymptomatic LQTS, 491±41 ms in symptomatic LQTS, and 498±49 ms in di-QTprol. Baseline EMW was 6±14 ms in controls, -12±29 ms in asymptomatic LQTS, -52±16 ms in symptomatic LQTS, and -5±69 ms in di-QTprol. Over years of follow-up, EMW remained stable in controls (8±10 ms; Fig. 1A) and the asymptomatic LQTS group (-17±20 ms; Fig. 1B). In LQTS patients with TdP/VF, EMW (baseline measured at -534 (-962 to -143) days before arrhythmia) had become profoundly more negative, -127±42 ms, (p=0.01 vs. baseline) at 1 (0 to 5) days after the arrhythmia and returned to basal values, -52±18 ms, (p=0.005) after 722 (155 to 3100) days (Fig. 1C). There was a significant correlation between time-to-event and EMW negativity (r=0.72, p0.0001), indicating stronger EMW negativity when measured closer to TdP/VF. For the di-QTprol patients (n=2 amiodarone; n=2 escitalopram; n=1 sotalol) a trend towards more exaggerated EMW negativity was observed: from baseline (at -19 (-785 to -13) days before the event) to -125±33 ms (p=0.08 vs. baseline) at 1 (1 to 5) days after TdP (Fig. 1D). Again, significant correlation was found between time-to-event and EMW negativity (r=0.6, p=0.03). Conclusion Episodes of electrical instability in patients with LQTS or di-QTprol are associated with profound but reversible exaggeration of EMW negativity. If also present just prior to TdP/VF (as in experimental models of torsadogenic di-QTprol and anecdotal LQTS cases), imminent ventricular arrhythmias may be anticipated as electromechanical reciprocity may contribute to arrhythmogenesis.Figure 1Graphical Abstract