Vox clamantis in deserto. We spoke but nobody was listening: echocardiography can help risk stratification of the long-QT syndrome.

Over 20 years ago we reported for the first time the presence of mechanical abnormalities in the contraction pattern of patients with the long QT syndrome (LQTS), showing the presence both of rapid early contraction and of an extended ‘plateau’ phase clearly visible at M-mode Doppler before rapid relaxation. These abnormalities were almost absent in controls and more prevalent among symptomatic than asymptomatic patients [77% vs. 19%, relative risk (RR) 2.75], suggesting their potential value for diagnosis and risk stratification of LQTS patients. This report and our subsequent evidence that these abnormalities were abolished by calcium blockers and could be the mechanical counterparts of early afterdepolarizations (EADs), thus being markers of arrhythmic propensity, were received with scepticism and essentially ignored. Eventually, an abnormal contraction pattern was confirmed by others, mostly using tissue Doppler imaging, 5 thus ending the era in which LQTS was considered a pure electrical disease. Once set in motion, the ball keeps rolling. Now ter Bekk et al. describe the presence of a negative ‘electromechanical window’ (EMW) in LQTS patients and report a strong association between a markedly negative value and arrhythmic events. One strength lies in the size of the population, almost 250 genotype-positive LQTS patients and 74 controls, much larger than previous studies. – 5 This allowed the authors to demonstrate conclusively that the vast majority of LQTS patients do have abnormal echocardiographic features, with approximately two-thirds of LQTS patients showing EMW values .2 SD below the values of controls, despite pharmacological treatment (found to reduce EMW negativity) in .40% of patients. This important study, carried out by three expert groups, shows that even in the era of intensive genotyping, echocardiography can provide valuable information, and within a few minutes. Importantly, the almost 100 patients with arrhythmic events allowed a reliable estimate of the sensitivity and specificity of the echocardiographic indexes and the execution of multivariable analyses. Adding EMW to QTc resulted in a significant improvement in the identification of symptomatic patients; EMW but not QTc was an independent predictor of arrhythmic events. This finding is in agreement with the demonstration by Haugaa et al. that echocardiographic contraction duration identified symptomatic patients with better sensitivity and specificity compared with QTc (79% and 74% vs. 70% and 50%, respectively), and with our original indication that echocardiography was superior to ECG. The time has come to start using echocardiographic indexes in addition to QTc in the risk stratification of patients with LQTS. It is unclear, however, which parameter performs best and, in this regard, neither the study by Haugaa et al. nor that by ter Bekk et al. is very helpful because the authors did not compare their index, EMW, with those previously described. –4 The use of EMW was suggested as a risk marker for Torsades des Pointes (TdP) in experimental studies, but its superiority to QTc has been questioned. The choice of the best mechanical index would be facilitated if we had a good understanding of the pathophysiology underlying the contraction and relaxation abnormalities present in LQTS patients. This is one weakness of the present study by ter Bekk et al. which suggests that LQTS patients may have enhanced lusitropy as a consequence of heterogeneous sympathetic activation. As a matter of fact, this is unlikely because LQTS patients actually show abnormally impaired rather that enhanced relaxation. Ranolazine, a late INa blocker, shortened QTc by 4.6% from 558+55 ms to 532 + 46 ms, and by a significant 13% a previously prolonged isovolumic relaxation time of 125+ 27 ms in 12 patients with LQT3, the LQTS subtype caused by enhanced late INa