Non-invasive testing of acquired long QT syndrome: Evidence for multiple arrhythmogenic substrates

Background: Although well-defined clinically and electrocardiographically, Acquired Long QT Syndrome (LQTS) remains elusive from a pathophysiologic po int of view. An increasingly accepted hypothesis is that it represents an a ttenuated form of Congenital Long QT Syndrome. To test this hypothesis furt her, we investigated patients with Acquired LQTS, using various investigati ons that are known to give information in patients with Congenital LQTS. Me thods: All the investigations were performed in patients with a history of Acquired Long QT Syndrome, defined by marked transient QT lengthening (QT>6 00 ms) and/or torsades de pointes. Measurement of the QT interval dispersio n, the interlead difference for the QT interval on a 12-lead EGG. was perfo rmed in 18 patients and compared with 18 controls, matched for age and sex. To assess sympathetic myocardial innervation, I-123 Meta-iodobenzylguanidi ne (I-123-MIBG) scintigraphy was performed in 12 patients, together with Th allium scintigraphy, to rule out abnormal myocardial perfusion. Time-freque ncy analysis of a high-resolution ECG using a wavelet technique, was made f or nine patients and compared with 38 healthy controls. Finally, genetic st udies were performed prospectively in 16 consecutive patients. to look for HERG, KCNE1, KCNE2 and KCNQ1 mutations. The functional profile of a mutated HERG protein was performed using the patch-clamp technique. Results: Compa red with the control group, a significant increase in QT dispersion was obs erved in the patients with a history of Acquired LQTS (55 +/- 15 vs. 33 +/- 9 ms, P<0.001). In another group of patients with Acquired LQTS, 123 I-MIBG tomoscintigraphy demonstrated a decrease in the sympathetic myocardial inn ervation, Time-frequency analysis using wavelet transform, demonstrated an abnormal frequency content within the QRS complexes, in the patients with A cquired LQTS, similar to that found in Congenital LQTS patients. Molecular screening in 16 consecutive patients, identified one patient with a missens e mutation on HERG, one of the LQTS genes. Expression of the mutated HERG p rotein led to altered K+ channel function. Conclusion: Our results suggest that Acquired and Congenital Long QT Syndromes have some common features. T hey allow the mechanism of the clinical heterogeneity, found in both syndro mes, to be understood. Further multi-facet approaches are needed to deciphe r the complex interplay between the main determinants of these arrhythmogen ic diseases. <(c)> 2001 Published by Elsevier Science B.V.