Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome.

Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome. Research Abstract Details 

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Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome. Abstract Text:

Jean-Philippe Couderc,Martino Vaglio,Xiajuan Xia,Scott McNitt,Pierre Wicker,Nenad Sarapa,Arthur J Moss,Wojciech Zareba,Jean-Philippe Couderc,Martino Vaglio,Xiajuan Xia,Scott McNitt,Pierre Wicker,Nenad Sarapa,Arthur J Moss,Wojciech Zareba,

INTRODUCTION: The QTc interval prolongation is not a perfect surrogate marker of the presence of an increased risk for arrhythmic events. In the search for alternative markers, we investigated the T-amplitude and QT interval adaptation to heart rate (HR) in patients with the congenital long QT syndrome (LQTS) and individuals with sotalol-induced QT prolongation. METHODS AND RESULTS: Our investigation is based on the analysis of continuous 12-lead digital Holter recordings in: 49 LQT1 carriers, 25 LQT2 carriers, 37 healthy individuals off drugs and on 160 mg of sotalol, and 21 of them also on 320 mg of sotalol. The Holter recordings were used to investigate repolarization parameters and their HR dependency. A loss of HR dependency of the T-amplitude was found as a common feature in individuals with impaired I(kr) kinetics: LQT2 carriers and subjects on sotalol. The T-amplitude/RR slope was significantly (P < 0.05) flatter in LQT2 (0.31 +/- 0.27 microV/ms) than in both LQT1 (0.62 +/- 0.40 microV/ms) and healthy individuals (0.55 +/- 0.29 microV/ms). A dose-dependent reduction of the T-amplitude/RR slope was also observed in subjects on sotalol (160 mg dose: 0.26 +/- 0.19 microV/ms; 320 mg dose: 0.21 +/- 0.14 microV/ms). The QT/RR slope was less effective than T-amplitude/RR slope in differentiating between congenital and drug-induced repolarization delay. CONCLUSIONS: Impaired adaptation of T-amplitude to changing HR is a common electrocardiographic feature associated with KCNH2 mutation and I(kr) blockade by sotalol. This ECG marker may play an important role in the future of the assessment of the penetrance of KCNH2 mutation and the identification of a drug effect on the I(kr) kinetics.

Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome. Publishing Authors By Initials

JP Couderc,M Vaglio,X Xia,S McNitt,P Wicker,N Sarapa,AJ Moss,W Zareba,JP Couderc,M Vaglio,X Xia,S McNitt,P Wicker,N Sarapa,AJ Moss,W Zareba,

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Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Journal of cardiovascular electrophysiology

VOLUME: 18

Page Numbers: 1299-305

Journal Abbreviation: J. Cardiovasc. Electrophysiol.

ISSN: 1540-8167

DAY: 4

MONTH: 10

YEAR: 2007

Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome. Information

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LANGUAGE: eng

NlmUniqueID: 9010756

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Grant and Affiliation Information for Impaired T-amplitude adaptation to heart rate characterizes I(Kr) inhibition in the congenital and acquired forms of the long QT syndrome.

AFFILIATION: Heart Research Follow-Up Program, Cardiology Department, University of Rochester Medical Center, Rochester, New York, USA. jean-philippe.couderc@heart.rochester.edu

Country: United States

AGENCY: United States NHLBI

GRANT: R01-HL 68226

ACRONYM: HL

MEDLINETA: J Cardiovasc Electrophysiol

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