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  • 1.
    Lundström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Autonomic cardiac control in long QT syndrome: clinical studies of arrhythmogenic triggers2024Doktoravhandling, med artikler (Annet vitenskapelig)
    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.

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  • 2.
    Lundström, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Eliasson, Håkan
    Karolinska Institutet, Institutionen för kvinnors och barns hälsa.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Holter study of heart rate variability in children and adolescents with long QT syndromeManuskript (preprint) (Annet vitenskapelig)
  • 3.
    Lundström, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för diagnostik och intervention.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Assessment of arrhythmias and heart rate response in healthy adolescents performing face immersion and body submersion in ice-cold waterManuskript (preprint) (Annet vitenskapelig)
  • 4.
    Lundström, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Law, Lucy
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Jensen, Steen M.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Aberrant autonomic pattern during the post-exercise recovery phase in long QT syndrome patients2021Inngår i: Autonomic Neuroscience: Basic & Clinical, ISSN 1566-0702, E-ISSN 1872-7484, Vol. 236, artikkel-id 102897Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [en]

    Objectives: It is well-established that the autonomic nervous system (ANS) plays a central role in arrhythmogenesis. During and after exercise the ANS is particularly active, and since long QT syndrome (LQTS) patients have an increased risk of lethal arrhythmias during physical activity, it is important to investigate the autonomic function in these patients. In this study we investigate the ANS response during and after exercise in LQTS patients and healthy age and sex matched controls.

    Methods: Forty-four genotype-verified adult LQTS patients and forty-four healthy age- and sex-matched controls performed a submaximal bicycle exercise stress test. Heart rate recovery (HRR) and heart rate variability (HRV) were analyzed from registered electrocardiogram (ECG) and vector electrocardiogram (VCG) recordings collected throughout rest, exercise and in the post-exercise phase.

    Results: LQTS patients had a slower HRR than controls at 1- and 4-min post-exercise (p < 0.001). During the post-exercise phase, LQTS patients had a lower total power (p < 0.001), low frequency power (p < 0.001) and high frequency power (p < 0.001) than controls. In the same phase, LQTS patients off betablocker (BB) treatment showed a lower high frequency power (p = 0.01) and different low frequency/high frequency ratio (p = 0.003) when comparing with LQTS patients on BB treatment.

    Conclusions: The parasympathetic effect on both HRR and HRV after exercise appears depressed in this LQTS patient cohort compared to healthy controls. This indicates an aberrant ANS response during the post-exercise phase which might be compensated by BB treatment. Our findings emphasize the importance of performing further investigations to identify the role of the ANS in LQTS arrhythmogenesis.

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  • 5.
    Lundström, Anna
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Department of Physiology, University of Auckland, Auckland, New Zealand.
    Eliasson, Håkan
    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Cardiac response to water activities in children with Long QT syndrome type 12023Inngår i: PLOS ONE, E-ISSN 1932-6203, Vol. 18, nr 12, artikkel-id e0295431Artikkel i tidsskrift (Fagfellevurdert)
    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.

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  • 6.
    Mörner, Stellan
    et al.
    Centrum för kardiovaskulär genetik, Hjärtcentrum, Norrlands universitetssjukhus, Umeå, Sverige.
    Carlberg, Bo
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Rydberg, Annika
    Centrum för kardiovaskulär genetik, Barn- och ungdomscentrum, Norrlands universitetssjukhus, Umeå, Sverige.
    Jensen, Steen M.
    Centrum för kardiovaskulär genetik, Hjärtcentrum, Norrlands universitetssjukhus, Umeå, Sverige.
    Lundström, Anna
    Centrum för kardiovaskulär genetik, Klinisk genetik, Laboratoriemedicin, Norrlands universitetssjukhus, Umeå, Sverige.
    Nyberg, Peter
    Centrum för kardiovaskulär genetik, Klinisk genetik, Laboratoriemedicin, Norrlands universitetssjukhus, Umeå.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Hellman, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Johnson, Owe
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Näslund, Ulf
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Ärftliga hjärt–kärlsjukdomar – ett multidisciplinärt arbetssätt krävs: [Experiences from a multidisciplinary cardiogenetic clinic]2021Inngår i: Läkartidningen, ISSN 0023-7205, E-ISSN 1652-7518, Vol. 118, nr 40, artikkel-id 21083Artikkel i tidsskrift (Fagfellevurdert)
    Abstract [sv]

    Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference.  In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.

  • 7.
    van der Crabben, Saskia N.
    et al.
    Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands.
    Mörner, Stellan
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands.
    Lundström, Anna
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands.
    Jonasson, Jenni
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik. European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands.
    Bikker, Hennie
    Department of Clinical Genetics, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands; European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands.
    Amin, Ahmad S.
    European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences Amsterdam University Medical Centers, University of Amsterdam, Heart Center, Amsterdam, Netherlands.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands.
    Wilde, Arthur A. M.
    European Reference Network for rare, low-prevalence, or complex diseases of the heart (ERN GUARD-Heart), Amsterdam, Netherlands; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences Amsterdam University Medical Centers, University of Amsterdam, Heart Center, Amsterdam, Netherlands.
    Should variants of unknown significance (VUS) be disclosed to patients in cardiogenetics or not; only in case of high suspicion of pathogenicity?2022Inngår i: European Journal of Human Genetics, ISSN 1018-4813, E-ISSN 1476-5438, Vol. 30, s. 1208-1210Artikkel i tidsskrift (Fagfellevurdert)
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