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Cardiac response to water activities in children with Long QT syndrome type 1
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
Umeå University, Faculty of Medicine, Department of Radiation Sciences, Radiation Physics.ORCID iD: 0000-0002-1313-0934
Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics. Department of Physiology, University of Auckland, Auckland, New Zealand.ORCID iD: 0000-0002-9323-3166
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
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2023 (English)In: PLOS ONE, E-ISSN 1932-6203, Vol. 18, no 12, article id e0295431Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Swimming is a genotype-specific trigger in long QT syndrome type 1 (LQT1).

OBJECTIVE: To examine the autonomic response to water activities in children and adolescents with LQT1.

METHODS: In this cross-sectional study, LQT1 patients were age and sex matched to one healthy control subject. Electrocardiograms (ECGs) were recorded during face immersion (FI), swimming, diving, and whole-body submersion (WBS). Heart rate (HR) and heart rate variability (HRV) was measured. The high frequency (HF) component of HRV was interpreted to reflect parasympathetic activity, while the low frequency (LF) component was interpreted as reflecting the combined influence of sympathetic and parasympathetic activity on autonomic nervous modulation of the heart.

RESULTS: Fifteen LQT1 patients (aged 7-19 years, all on beta-blocker therapy) and fifteen age and sex matched non-medicated controls were included. No significant ventricular arrhythmias were observed in the LQT1 population during the water activities. Out of these 15 matched pairs, 12 pairs managed to complete FI and WBS for more than 10 seconds and were subsequently included in HR and HRV analyses. In response to FI, the LQT1 group experienced a drop in HR of 48 bpm, compared to 67 bpm in the control group (p = 0.006). In response to WBS, HR decreased by 48 bpm in the LQT1 group and 70 bpm in the control group (p = 0.007). A significantly lower PTOT (p < 0.001) and HF (p = 0.011) component was observed before, during and after FI in LQT1 patients compared with the controls. Before, during and after WBS, a significantly lower total power (p < 0.001), LF (p = 0.002) and HF (p = 0.006) component was observed in the LQT1 patients.

CONCLUSION: A significantly lower HR decrease in response to water activities was observed in LQT1 subjects on beta-blocker therapy, compared to matched non-medicated controls. The data suggests an impaired parasympathetic response in LQT1 children and adolescents. An aberrant autonomic nervous system (ANS) response may cause an autonomic imbalance in this patient group.

Place, publisher, year, edition, pages
Public Library of Science (PLoS), 2023. Vol. 18, no 12, article id e0295431
National Category
Cardiac and Cardiovascular Systems
Identifiers
URN: urn:nbn:se:umu:diva-218679DOI: 10.1371/journal.pone.0295431PubMedID: 38060596Scopus ID: 2-s2.0-85179900660OAI: oai:DiVA.org:umu-218679DiVA, id: diva2:1822780
Available from: 2023-12-27 Created: 2023-12-27 Last updated: 2024-03-27Bibliographically approved
In thesis
1. Autonomic cardiac control in long QT syndrome: clinical studies of arrhythmogenic triggers
Open this publication in new window or tab >>Autonomic cardiac control in long QT syndrome: clinical studies of arrhythmogenic triggers
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Alternative title[sv]
Autonom kardiell kontroll vid långt QT syndrom : kliniska studier av arytmogena faktorer
Abstract [en]

Background: Long QT syndrome (LQTS) is an inherited cardiac disease characterized by prolonged cardiac repolarization and an increased risk for life-threatening arrhythmias. These arrhythmias are typically triggered by adrenergic stimuli, such as physical activity and intense emotions, implicating that the sympathetic part of the autonomic nervous system (ANS) is involved in arrhythmogenesis. However, symptoms also commonly occur swimming and diving, situations associated with dual activation of both branches of the ANS. This observation suggests that both sympathetic and parasympathetic physiological responses may contribute to the initiation of arrhythmias in individuals with LQTS.

Aim: The overall aim of this thesis was to describe the cardiac autonomic response in LQTS patients during daily activities, exercise, and swimming, as well as to assess the presence of arrhythmias during activities in water. 

Methods: In all 4 studies electrocardiograms (ECGs) were recorded. In study I and II, a 24-hour ECG (Holter) system was used. In study III and IV, a waterproof 2-lead ECG device (Actiwave-Cardio) was used. In study I, ECGs were collected from adult LQTS patients (n = 44) and healthy controls (n = 44) during a submaximal bicycle exercise stress test. In study II, annual 24-hour ECG recordings (n = 575) during ordinary daily living was retrospectively collected in children with LQTS (n = 116). In study III, children with LQTS type 1 (LQT1) (n = 15) and age and sex matched healthy controls (n = 15) performed face immersion (FI), swimming, diving, and whole-body submersion (WBS). In study IV, healthy adolescents aged 15 years performed FI (n = 54) and ice-water immersion (IWI) of the body (n = 20).

Heart rate responses and spectral analysis of heart rate variability (HRV) were assessed. HRV measures the beat-to-beat variation of the RR intervals of the heart, making it possible to non-invasively analyze the cardiac autonomic influence on the heart. The total power (PTOT) reflects all the variation during the recorded period. The high frequency (HF) component reflects parasympathetic activity, while the low frequency (LF) is influenced by both the sympathetic and parasympathetic activity.

Results: In study I, LQTS patients had a decreased heart rate reduction and a lower PTOT, LF and HF than controls during the post-exercise phase. LQTS patients off beta-blocker (BB) treatment showed a lower HF and higher LF/HF ratio compared to LQTS patients on BB treatment. In study II, a correlation between heart rate and changes in HRV parameters was observed. At higher heart rates, the whole cohort of LQTS patients, as well as the subgroup of LQTS patients off BB, had lower HRV values than controls. A pattern was observed indicating that LQT1 patients had lower HF in the age group of 1-10 years, with this trend shifting as age increased, resulting in lower HF in the LQT2 patients aged 15-18 years. LQT1 girls aged 10-18 years had lower PTOT than LQT1 boys. Study III showed that LQT1 patients had a smaller reduction in heart rate during FI and WBS than controls. LQT1 patients had a lower HRV before, during and after FI and WBS than controls. In study IV, in healthy adolescents, supraventricular extrasystoles were relatively common during both FI and IWI, and 2 of 54 had ventricular bigeminy during FI. FI resulted in a more pronounced heart rate reduction compared to IWI.

Conclusions: The results of these studies indicate that individuals with LQTS have an aberrant cardiac response to activities that affects the ANS. After exercise and in response to water activities, the parasympathetic effect on both the heart rate and HRV appears depressed in LQTS patients. Additionally, during everyday activities, LQTS patients generally have lower HRV values at higher heart rates compared to controls. These findings suggest that both branches of the ANS might be involved in arrhythmogenesis in this patient group, and that an increased understanding of the ANS role could improve patient management and treatment. 

The results from the ice-water study indicate that the ventricular arrhythmia risk is likely higher during whole-body submersion with apnea. The absence of arrhythmias in beta-blocked LQT1 patients indicates effective protection by their current treatment.

Place, publisher, year, edition, pages
Umeå: Umeå University, 2024. p. 96
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 2287
Keywords
Long QT syndrome, pediatrics, exercise, Holter, water immersion, arrhythmia, clinical physiology, ECG, heart rate variability, heart rate response
National Category
Cardiac and Cardiovascular Systems Pediatrics Physiology
Research subject
cardiovascular disease; Cardiology; Pediatrics
Identifiers
urn:nbn:se:umu:diva-222782 (URN)978-91-8070-302-4 (ISBN)978-91-8070-301-7 (ISBN)
Public defence
2024-04-26, Sal D, 9 trappor, Norrlands Universitetssjukhus, Umeå, 09:00 (Swedish)
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Supervisors
Available from: 2024-04-08 Created: 2024-03-27 Last updated: 2024-03-28Bibliographically approved

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Lundström, AnnaWiklund, UrbanWinbo, AnnikaKarlsson, MarcusRydberg, Annika

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