Copyright © 2001 by the European Society of Cardiology.
Dynamic analysis of the QT interval in long QT1 syndrome patients with a normal phenotype
a INSERM U533, Hôpital Hôtel-Dieu, Nantes, France
b Service de Cardiologie, Centre Hospitalier Universitaire de Rennes, Rennes, France
c Service de Cardiologie, Centre Hospitalier Universitaire de Nantes, Nantes, France
revised May 22, 2000; accepted May 24, 2000
Abstract
Aims In families with the long QT syndrome penetrance may be low: up to 70% of gene carriers may have a normal QTc interval. These patients require therapy, similar to that in those with longer QTc intervals, but identifying them, using molecular analysis, is difficult to apply on a large scale. A large French family affected by the long QT1 syndrome was followed-up over a 25-year period. In adult males but not in females, the QTc interval normalized after puberty. We aimed to find clinical criteria, based on ambulatory ECG recordings so that we could improve diagnosis in affected members with a normal QTc.
Methods and Results Linkage analysis and direct sequencing were an indicator of the long QT1 gene in our family. Reverse transcription-polymerase chain reaction analysis demonstrated abnormal transcripts in lymphocytes from silent gene carriers. The functional profile of mutated protein isoforms was investigated using the patch–clamp technique. Dynamic analysis of ventricular depolarization was conducted using Holter recordings in patients, and in sex- and age-matched controls. Circadian variations of the QTc interval and the QT/RR relationship were assessed. Sensitivity, specificity, and predictive values were evaluated for proposed clinical criteria. We found that dynamic analysis of the QT interval permitted individual diagnosis in mutation carriers even when the QTc interval was normal (adult males).
Conclusion Dynamic analysis of the QT interval is of diagnostic value in the long QT1 syndrome in patients with a normal phenotype. Clinical implications include improvement in screening and patient management.
Key Words: Long QT syndrome, KvLQT1, ambulatory ECG recording, QT dynamic
f2 Correspondence: Dr Gilles Lande, INSERM U533, 1 rue Gaston Veil, B.P. 53508, 44093 Nantes Cedex 1, France.
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