Repolarization studies in the long QT syndrome
Abstract
ABSTRACT
Background: Sudden cardiac death in the young is predominantly caused by inherited cardiac conditions. Long QT syndrome (LQTS) is one of the most common of these disorders. Since risk stratification relies largely upon the heart rate (HR) corrected QT interval (QTc), it is crucial to identify an appropriate method for QT correction. Furthermore, cardiac events in LQTS type 1 (LQT1) occur commonly at HR increase. Repolarization duration and dispersion was therefore studied at HR increase.
Aims: The objectives were to describe the electrocardiographic and vectorcardiographic phenotype in LQTS patients and to compare repolarization response including dispersion to HR increase between LQT1 and healthy controls.
Methods: Paper I compared four different methods for HR correction of the QT interval in a group of LQTS patients using linear regression. In a subgroup, comparisons were made before and after the initiation of betablockers. In paper II and IV we used an intravenous bolus injection of atropine to increase HR in LQT1 patients and healthy controls. Vectorcardiography (VCG) was continuously recorded and VCG parameters were compared. Paper III compared the VCG reaction to increased HR induced by an exercise stress test in LQT1 patients and healthy controls.
Results: Bazett´s method yielded the only correction resulting in a QTc without relation to HR, irrespective of initiation of betablockers. Although a similar HR response to atropine, the QT adaptation was faster in LQT1 than in healthy controls. As a response to exercise, the QTcB and its components, the HR corrected QTpeak and Tpeak-end intervals, but not global dispersion parameters, separated LQT1 patients from controls.
Following a rapid HR increase induced by atropine, the majority in both groups showed a biphasic response for global measures of VR dispersion, including an overshoot; in LQT1 the overshoot was more pronounced.
Conclusions: Although questioned, Bazett´s method remains preferable for QT correction in LQT1 and 2. Faster QT adaptation following a rapid HR increase in LQT1 patients indicates a disturbed QT hysteresis. Timing of repolarization duration but not global dispersion parameters distinguished LQT1 patients from controls after exercise. The biphasic response in VR dispersion was exaggerated in LQT1 patients which could play a role in arrhythmogenesis, but further studies are warranted.
Parts of work
I. Dahlberg P, Diamant U-B, Gilljam T, Rydberg A, Bergfeldt L. QT correction using Bazett´s formula remains preferable in long QT syndrome type 1 and 2. Ann Noninvasive Electrocardiol. 2021 Jan;26(1):e12804.
https://doi.org/10.1111/anec.12804 II. Dahlberg P*, Axelsson KJ*, Jensen SM, Lundahl G, Vahedi F, Gransberg L, Bergfeldt L. Accelerated QT adaptation following atropine-induced heart rate increase in LQT1 patients versus healthy controls: A sign of disturbed hysteresis. Physiol Rep. 2022 Nov;10(21):e15487.
https://doi.org/10.14814/phy2.15487 III. Dahlberg P, Axelsson KJ, Rydberg A, Lundahl G, Gransberg L, Bergfeldt L. Spatio-temporal repolarization dispersion before and after exercise in patients with long QT syndrome type 1 vs controls. AJP - Heart and Circulatory Physiology. September 2023
https://doi.org/10.1152/ajpheart.00335.2023 IV. Dahlberg P, Axelsson KJ, Jensen SM, Lundahl G, Gransberg L, Bergfeldt L. Greater overshoot in the adaptation of repolarization dispersion following atropine-induced heart rate increase in LQT1 patients and healthy controls. Manuscript
Degree
Doctor of Philosophy (Medicine)
University
University of Gothenburg. Sahlgrenska Academy
Institution
Institute of Medicine. Department of Molecular and Clinical Medicine
Disputation
Fredagen den 17 november 2023, kl 9.00, Hjärtats aula, Vita stråket 12, Sahlgrenska universitetssjukhuset, Göteborg
Date of defence
2023-11-17
pia.i.dahlberg@vgregion.se
Date
2023-10-26Author
Dahlberg, Pia
Keywords
long QT syndrome
repolarization
hysteresis
vectorcardiography
QT adaptation
ventricular repolarization
Publication type
Doctoral thesis
ISBN
978-91-8069-449-0 (TRYCK)
978-91-8069-450-6 (PDF)
Language
eng