title: Non-invasive testing of acquired long QT syndrome: evidence for multiple arrhythmogenic substrates.
abstract: BACKGROUND
  Although well-defined clinically and electrocardiographically, Acquired Long QT Syndrome (LQTS) remains elusive from a pathophysiologic point of view. An increasingly accepted hypothesis is that it represents an attenuated form of Congenital Long QT Syndrome. To test this hypothesis further, we investigated patients with Acquired LQTS, using various investigations that are known to give information in patients with Congenital LQTS.
  
  
  METHODS
  All the investigations were performed in patients with a history of Acquired Long QT Syndrome, defined by marked transient QT lengthening (QT>600 ms) and/or torsades de pointes. Measurement of the QT interval dispersion, the interlead difference for the QT interval on a 12-lead ECG, was performed in 18 patients and compared with 18 controls, matched for age and sex. To assess sympathetic myocardial innervation, I-123 Meta-iodobenzylguanidine (I-123-MIBG) scintigraphy was performed in 12 patients, together with Thallium scintigraphy, to rule out abnormal myocardial perfusion. Time-frequency analysis of a high-resolution ECG using a wavelet technique, was made for nine patients and compared with 38 healthy controls. Finally, genetic studies 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
  Compared with the control group, a significant increase in QT dispersion was observed 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 innervation. Time--frequency analysis using wavelet transform, demonstrated an abnormal frequency content within the QRS complexes, in the patients with Acquired LQTS, similar to that found in Congenital LQTS patients. Molecular screening in 16 consecutive patients, identified one patient with a missense mutation on HERG, one of the LQTS genes. Expression of the mutated HERG protein led to altered K(+) channel function.
  
  
  CONCLUSIONS
  Our results suggest that Acquired and Congenital Long QT Syndromes have some common features. They allow the mechanism of the clinical heterogeneity, found in both syndromes, to be understood. Further multi-facet approaches are needed to decipher the complex interplay between the main determinants of these arrhythmogenic diseases.
authors.affiliation: Département de Cardiologie et de Soins Intensifs, Hôpital Louis Pradel, Lyon, France.
authors.forename: P
authors.initials: P
authors.lastname: Chevalier
authors.forename: C
authors.initials: C
authors.lastname: Rodriguez
authors.forename: L
authors.initials: L
authors.lastname: Bontemps
authors.forename: M
authors.initials: M
authors.lastname: Miquel
authors.forename: G
authors.initials: G
authors.lastname: Kirkorian
authors.forename: R
authors.initials: R
authors.lastname: Rousson
authors.forename: F
authors.initials: F
authors.lastname: Potet
authors.forename: J J
authors.initials: JJ
authors.lastname: Schott
authors.forename: I
authors.initials: I
authors.lastname: Baró
authors.forename: P
authors.initials: P
authors.lastname: Touboul
mesh_terms: D000368:Aged; D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D051638:Ether-A-Go-Go Potassium Channels; D005260:Female; D006321:Heart / Q000294:innervation; D006801:Humans; D008133:Long QT Syndrome / Q000139:chemically induced / Q000151:congenital / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D015221:Potassium Channels / Q000235:genetics; D024642:Potassium Channels, Voltage-Gated; D011446:Prospective Studies; D013564:Sympathetic Nervous System / Q000503:physiopathology; D014055:Tomography, Emission-Computed; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG
chemical_list: D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG