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  • 1.
    Abdelsayed, Mena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Bytyci, Ibadete
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Universi College, Bardhosh, Prishtina, Kosovo.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Molecular and Clinical Sciences Research Institute, St George University London, UK; Institute of Fluid Dynamics, Brunel University, London, UK.
    Left Ventricular Contraction Duration Is the Most Powerful Predictor of Cardiac Events in LQTS: A Systematic Review and Meta-Analysis2020Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 9, nr 9, artikel-id 2820Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Background: Long-QT syndrome (LQTS) is primarily an electrical disorder characterized by a prolonged myocardial action potential. The delay in cardiac repolarization leads to electromechanical (EM) abnormalities, which adds a diagnostic value for LQTS. Prolonged left ventricular (LV) contraction was identified as a potential risk for arrhythmia. The aim of this meta-analysis was to assess the best predictor of all EM parameters for cardiac events (CEs) in LQTS patients. Methods: We systematically searched all electronic databases up to March 2020, to select studies that assessed the relationship between echocardiographic indices—contraction duration (CD), mechanical dispersion (MD), QRS onset to peak systolic strain (QAoC), and the EM window (EMW); and electrical indices— corrected QT interval (QTC), QTC dispersion, RR interval in relation to CEs in LQTS. This meta-analysis included a total of 1041 patients and 373 controls recruited from 12 studies. Results: The meta-analysis showed that LQTS patients had electrical and mechanical abnormalities as compared to controls—QTC, WMD 72.8; QTC dispersion, WMD 31.7; RR interval, WMD 91.5; CD, WMD 49.2; MD, WMD 15.9; QAoC, WMD 27.8; and EMW, WMD −62.4. These mechanical abnormalities were more profound in symptomatic compared to asymptomatic patients in whom disturbances were already manifest, compared to controls. A CD ≥430 ms had a summary sensitivity (SS) of 71%, specificity of 84%, and diagnostic odds ratio (DOR) >19.5 in predicting CEs. EMW and QTC had a lower accuracy. Conclusions: LQTS is associated with pronounced EM abnormalities, particularly prolonged LV myocardial CD, which is profound in symptomatic patients. These findings highlight the significant role of EM indices like CD in managing LQTS patients.

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  • 2. Acuña Mora, Mariela
    et al.
    Sparud-Lundin, Carina
    Burström, Åsa
    Hanseus, Katarina
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Moons, Philip
    Bratt, Ewa-Lena
    Patient empowerment and its correlates in young persons with congenital heart disease2019Ingår i: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 18, nr 5, s. 389-398, artikel-id 1474515119835434Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE:: The objective of this study was to measure the level of empowerment and identify its correlates in young persons with congenital heart disease.

    STUDY DESIGN:: Patients aged 14-18 years with congenital heart disease, and under active follow-up in one of four paediatric cardiology centres in Sweden were invited to participate in a cross-sectional study. A total of 202 young persons returned the questionnaires. Patient empowerment was measured with the Gothenburg Young Persons Empowerment Scale that allows the calculation of total and subscale scores. Univariate and multivariate linear regression analyses were undertaken to analyse possible correlates, including: sex, age, health behaviours, knowledge of congenital heart disease, quality of life, patient-reported health, congenital heart disease complexity, transition readiness and illness perception.

    RESULTS:: The mean empowerment score was 54.6±10.6 (scale of 15-75). Univariate analyses showed that empowerment was associated with age, quality of life, transition readiness, illness perception, health behaviours and patient-reported health (perceived physical appearance, treatment anxiety, cognitive problems and communication issues). However, multivariable linear regression analyses identified that only transition readiness (β=0.28, P<0.001) and communication (β=0.36, P<0.001) had a positive association with patient empowerment. These variables were also significantly associated with the subscale scores of the empowerment scale of knowledge and understanding ( P<0.001), shared decision-making ( P<0.001) and enabling others ( P<0.01). The overall models' explained variance ranged from 8% to 37%.

    CONCLUSION:: Patient empowerment was associated with transition readiness and fewer problems communicating. While it is not possible to establish the directionality of the associations, interventions looking to increase empowerment could benefit from using these variables (or measurements) for evaluation purposes.

  • 3.
    Acuña Mora, Mariela
    et al.
    Institute of Health and Care Sciences, University of Gothenburg, Gothenburg, Sweden; Faculty of Caring Science, Work Life and Social Welfare, University of Borås, Borås, Sweden.
    Sparud-Lundin, Carina
    Institute of Health and Care Sciences, University of Gothenburg, Gothenburg, Sweden.
    Fernlund, Eva
    Division of Pediatrics, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Crown Princess Victoria Children's Hospital, Linköping University Hospital, Linköping, Sweden.
    Fadl, Shalan
    Department of Children and Young Adults, University Hospital Örebro, Sweden.
    Kalliopi, Kazamia
    Department of Women's and Children's Health, Karolinska Institute, Stockholm, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Burström, Åsa
    Karolinska Institute, Department of Neurobiology, Care Sciences and Society, Stockholm, Sweden.
    Hanseus, Katarina
    Children's Heart Center, Skåne University Hospital Lund, Lund, Sweden.
    Moons, Philip
    Institute of Health and Care Sciences, University of Gothenburg, Gothenburg, Sweden; Department of Public Health and Primary Care, KU Leuven, Leuven, Belgium; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
    Bratt, Ewa-Lena
    Institute of Health and Care Sciences, University of Gothenburg, Gothenburg, Sweden; Department of Pediatric Cardiology, Queen Silvia Children's Hospital, Gothenburg, Sweden.
    The longitudinal association between patient empowerment and patient-reported outcomes: what is the direction of effect?2022Ingår i: PLOS ONE, E-ISSN 1932-6203, Vol. 17, nr 11, artikel-id e0277267Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Theoretical literature and cross-sectional studies suggest empowerment is associated with other patient-reported outcomes (PROs). However, it is not known if patient empowerment is leading to improvements in other PROs or vice versa. AIMS: The present study aimed to examine the direction of effects between patient empowerment and PROs in young persons with congenital heart disease (CHD). METHODS: As part of the STEPSTONES-CHD trial, adolescents with CHD from seven pediatric cardiology centers in Sweden were included in a longitudinal observational study (n = 132). Data were collected when patients were 16 (T0), 17 (T1) and 18 ½ years old (T2). The Gothenburg Young Persons Empowerment Scale (GYPES) was used to measure patient empowerment. Random intercepts cross-lagged panel models between patient empowerment and PROs (communication skills; patient-reported health; quality of life; and transition readiness) were undertaken. RESULTS: We found a significant cross-lagged effect of transition readiness over patient empowerment between T1 and T2, signifying that a higher level of transition readiness predicted a higher level of patient empowerment. No other significant cross-lagged relationships were found. CONCLUSION: Feeling confident before the transition to adult care is necessary before young persons with CHD can feel in control to manage their health and their lives. Clinicians interested in improving patient empowerment during the transitional period should consider targeting transition readiness.

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  • 4.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Handheld ECG in analysis of arrhythmia and heart rate variability in children with Fontan circulation2014Ingår i: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 47, nr 3, s. 374-382Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Our aim was to evaluate the intermittent use of a handheld ECG system for detecting silent arrhythmias and cardiac autonomic dysfunction in children with univentricular hearts. Methods: Twenty-seven patients performed intermittent ECG recordings with handheld devices during a 14-day period. A manual arrhythmia analysis was performed. We analyzed heart rate variability (HRV) using scatter plots of all interbeat intervals (Poincare plots) from the total observation period. Reference values of HRV indices were determined from Holter-ECGs in 41 healthy children. Results: One asymptomatic patient had frequent ventricular extra systoles. Another patient had episodes with supraventricular tachycardia (with concomitant palpitations). Seven patients showed reduced HRV. Conclusions: Asymptomatic arrhythmia was detected in one patient. The proposed method for pooling of intermittent recordings from handheld or similar devices may be used for detection of arrhythmias as well as for cardiac autonomic dysfunction.

  • 5.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Strömvall-Larsson, Eva
    Division of Cardiology, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Berggren, Håkan
    Division of Cardiothoracic Surgery, Department of Paediatrics, Sahlgrenska University Hospital/Queen Silvia Children’s Hospital, Göteborg University, Göteborg, Sweden.
    Hanseus, Katarina
    Department of Paediatrics, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Johansson, Sune
    Paediatric Cardiac Surgical Unit, Children’s Hospital, Lund University Hospital, Lund, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Heart rate variability in children with fontan circulation: lateral tunnel and extracardiac conduit2012Ingår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 33, nr 2, s. 307-315Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The technique in Fontan surgery has developed from the lateral tunnel (LT) toward the extracardiac conduit (EC) used to reduce long-term complications such as atrial arrhythmia and sinus node dysfunction. Heart rate variability (HRV) examines cardiac nervous activity controlling the sinus node. This study aimed to investigate HRV in a cohort of children with univentricular hearts, focusing on the relation between HRV and surgical procedure. For 112 children with Fontan circulation, HRV was analyzed using power spectral analysis. Spectral power was determined in three regions: very-low-frequency (VLF), low-frequency (LF), and high-frequency (HF) regions. Patients were compared with 66 healthy controls subject. Patients with LT were compared with patients who had EC. The children with Fontan circulation showed a significantly reduced HRV including total power (P < 0.0001), VLF (P < 0.0001), LF (P < 0.0001), and HF (P = 0.001) compared with the control subjects. The LT and EC patients did not differ significantly. Reduced HRV was found in both the LT and EC patients. In terms of HRV reduction, EC was not superior to LT.

  • 6.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sunnegårdh, Jan
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Hanséus, Katarina
    Department of Clinical Sciences Lund, Children Heart Center, Skåne University Hospital, Lund University, Lund, Sweden.
    Strömvall Larsson, Eva
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Nygren, Anders
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Dalén, Magnus
    Department of Molecular Medicine and Surgery, Department of Cardiac Surgery, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Berggren, Håkan
    Department of Pediatric Cardiac Surgery, Children's Heart Center, The Queen Silvia Children's Hospital, Gothenburg , Sweden.
    Johansson Ramgren, Jens
    Department of Pediatric Cardiac Surgery, Children´s Heart Center, Skånes University Hospital Lund, Sweden.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Pacemaker treatment after Fontan surgery: a Swedish national study2019Ingår i: Congenital Heart Disease, ISSN 1747-079X, E-ISSN 1747-0803, Vol. 14, nr 4, s. 582-589Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objective: Fontan surgery is performed in children with univentricular heart defects. Previous data regarding permanent pacemaker implantation frequency and indications in Fontan patients are limited and conflicting. We examined the prevalence of and risk factors for pacemaker treatment in a consecutive national cohort of patients after Fontan surgery in Sweden.

    Methods: We retrospectively reviewed all Swedish patients who underwent Fontan surgery from 1982 to 2017 (n = 599).

    Results: After a mean follow‐up of 12.2 years, 13% (78/599) of the patients with Fontan circulation had received pacemakers. Patients operated with the extracardiac conduit (EC) type of total cavopulmonary connection had a significantly lower prevalence of pacemaker implantation (6%) than patients with lateral tunnel (LT; 17%). Mortality did not differ between patients with (8%) and without pacemaker (5%). The most common pacemaker indication was sinus node dysfunction (SND) (64%). Pacemaker implantation due to SND was less common among patients with EC. Pacemaker implantation was significantly more common in patients with mitral atresia (MA; 44%), double outlet right ventricle (DORV; 24%) and double inlet left ventricle (DILV; 20%). In contrast, patients with pulmonary atresia with intact ventricular septum and hypoplastic left heart syndrome were significantly less likely to receive a pacemaker (3% and 6%, respectively).

    Conclusions: Thirteen percent of Fontan patients received a permanent pacemaker, most frequently due to SND. EC was associated with a significantly lower prevalence of pacemaker than LT. Permanent pacemaker was more common in patients with MA, DORV, and DILV.

  • 7.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hanséus, Katarina
    Department of Clinical Sciences Lund, Children Heart Centre, Skåne University Hospital, Lund University, Lund, Sweden.
    Strömvall Larsson, Eva
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Johansson Ramgren, Jens
    Department of Pediatric Cardiac Surgery, Children´s Heart Center, Skånes University Hospital Lund, Sweden.
    Berggren, Håkan
    Department of Pediatric Cardiac Surgery, Children's Heart Center, The Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Changes in Heart Rate and Heart Rate Variability During Surgical Stages to Completed Fontan Circulation2021Ingår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 42, nr 5, s. 1162-1169Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Arrhythmia is related to heart rate variability (HRV), which reflects the autonomic nervous regulation of the heart. We hypothesized that autonomic nervous ganglia, located at the junction of the superior vena cava’s entrance to the heart, may be affected during the bidirectional Glenn procedure (BDG), resulting in reduced HRV. We aimed to investigate changes in heart rate and HRV in a cohort of children with univentricular heart defects, undergoing stepwise surgery towards total cavopulmonary connection (TCPC), and compare these results with healthy controls. Twenty four hours Holter-ECG recordings were obtained before BDG (n = 47), after BDG (n = 47), and after total cavopulmonary connection (TCPC) (n = 45) in patients and in 38 healthy controls. HRV was analyzed by spectral and Poincaré methods. Age-related z scores were calculated and compared using linear mixed effects modeling. Total HRV was significantly lower in patients before BDG when compared to healthy controls. The mean heart rate was significantly reduced in patients after BDG compared to before BDG. Compared to healthy controls, patients operated with BDG had significantly reduced heart rate and reduced total HRV. Patients with TCPC showed reduced heart rate and HRV compared with healthy controls. In patients after TCPC, total HRV was decreased compared to before TCPC. Heart rate was reduced after BDG procedure, and further reductions of HRV were seen post-TCPC. Our results indicate that autonomic regulation of cardiac rhythm is affected both after BDG and again after TCPC. This may be reflected as, and contribute to, postoperative arrhythmic events.

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  • 8.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper.
    Hanséus, Katarina
    Department of Clinical Sciences Lund, Children Heart Centre, Skåne University Hospital, Lund University, Lund, Sweden.
    Strömvall Larsson, Eva
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Nygren, Anders
    Department of Cardiology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Institute of Clinical Sciences, Gothenburg University, Gothenburg, Sweden.
    Eliasson, Håkan
    Department of Women's and Children's Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sinus node dysfunction in patients with Fontan circulation: could heart rate variability be a predictor for pacemaker implantation?Manuskript (preprint) (Övrigt vetenskapligt)
  • 9.
    Alenius Dahlqvist, Jenny
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Karlsson, Marcus
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hanséus, Katarina
    Strömvall-Larsson, Eva
    Nygren, Anders
    Eliasson, Håkan
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sinus node dysfunction in patients with Fontan circulation: could heart rate variability be a predictor for pacemaker implantation?2019Ingår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 40, nr 4, s. 685-693Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Sinus node dysfunction (SND) causes significant morbidity in patients after Fontan surgery. Heart rate variability (HRV) reflects the autonomic regulation of the heart, and changes in HRV have been associated with SND in adults. We aimed to study whether changes in HRV could be detected in 24-h electrocardiographic (ECG) recordings in Fontan patients with SND. We compared HRV results from two patient groups; patients with Fontan circulation who later required a pacemaker due to severe SND (n = 12) and patients with Fontan circulation and SND, without indication for pacemaker treatment (n = 11), with two control groups; patients with Fontan circulation without SND (n = 90) and healthy controls (n = 66). The Poincare plot index SD2 (representing changes in heart rate over 24-h) and the very low-frequency (VLF) HRV component were significantly higher in both SND groups, both compared with healthy controls and patients with Fontan circulation without SND. In SND patients with pacemakers, SD2 and VLF were slightly reduced compared to SND patients without pacemaker (p = 0.06). In conclusion, in Fontan patients with SND the HRV is significantly higher compared to healthy controls and Fontan patients without SND. However, in patients with severe SND requiring pacemaker, SD2 and VLF tended to be lower than in patients with SND without pacemaker, which could indicate a reduced diurnal HRV in addition to the severe bradycardia. This is a small study, but our results indicate that HRV analysis might be a useful method in the follow-up of Fontan patients regarding development of SND.

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  • 10. Ambrosi, Aurelie
    et al.
    Salomonsson, Stina
    Eliasson, Håkan
    Zeffer, Elisabeth
    Dzikaite, Vijole
    Bergman, Gunnar
    Fernlund, Eva
    Theander, Elke
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Öhman, Annika
    Skogh, Thomas
    Rantapää-Dahlqvist, Solbritt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Reumatologi.
    Fored, Michael
    Blomqvist, Paul
    Ekbom, Anders
    Lindström, Ulla
    Melander, Mats
    Winqvist, Ola
    Gadler, Fredrik
    Jonzon, Anders
    Sonesson, Sven-Erik
    Wahren-Herlenius, Marie
    Influence of season of birth and maternal age in the development of congenital heart block in anti-Ro-SSA/La-SSB positive pregnancies2010Ingår i: Scandinavian Journal of Immunology, ISSN 0300-9475, E-ISSN 1365-3083, Vol. 72, nr 3, s. 265-Artikel i tidskrift (Refereegranskat)
  • 11. Ambrosi, Aurélie
    et al.
    Salomonsson, Stina
    Eliasson, Håkan
    Zeffer, Elisabeth
    Skog, Amanda
    Dzikaite, Vijole
    Bergman, Gunnar
    Fernlund, Eva
    Tingström, Joanna
    Theander, Elke
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Skogh, Thomas
    Öhman, Annika
    Lundström, Ulla
    Mellander, Mats
    Winqvist, Ola
    Fored, Michael
    Ekbom, Anders
    Alfredsson, Lars
    Källberg, Henrik
    Olsson, Tomas
    Gadler, Fredrik
    Jonzon, Anders
    Kockum, Ingrid
    Sonesson, Sven-Erik
    Wahren-Herlenius, Marie
    Development of heart block in children of SSA/SSB-autoantibody-positive women is associated with maternal age and displays a season-of-birth pattern2012Ingår i: Annals of the Rheumatic Diseases, ISSN 0003-4967, E-ISSN 1468-2060, Vol. 71, nr 3, s. 334-340Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVE: Congenital heart block may develop in the fetuses of Ro/SSA-positive and La/SSB-positive mothers. Recurrence rates of only 10-20% despite persisting maternal antibodies indicate that additional factors are critical for the establishment of heart block. The authors investigated the influence of other maternal and fetal factors on heart block development in a Swedish population-based cohort.

    METHODS: The influence of fetal gender, maternal age, parity and time of birth on heart block development was analysed in 145 families, including Ro/La-positive (n=190) and Ro/La-negative (n=165) pregnancies.

    RESULTS: There was a recurrence rate of 12.1% in Ro/La-positive women, and no recurrence in Ro/La-negative women. Fetal gender and parity did not influence the development of heart block in either group. Maternal age in Ro/La-positive pregnancies with a child affected by heart block was, however, significantly higher than in pregnancies resulting in babies without heart block (p<0.05).Seasonal timing of pregnancy influenced the outcome. Gestational susceptibility weeks 18-24 occurring during January-March correlated with a higher proportion of children with heart block and lower vitamin D levels during the same period in a representative sample of Swedish women and a corresponding higher proportion of children with heart block born in the summer (p<0.02). Maternal age or seasonal timing of pregnancy did not affect the outcome in Ro/La-negative pregnancies.

    CONCLUSION: This study identifies maternal age and seasonal timing of pregnancy as novel risk factors for heart block development in children of Ro/La-positive women. These observations may be useful for counselling when pregnancy is considered.

  • 12. Berghammer, Malin C
    et al.
    Brink, Eva
    Rydberg, Annika M
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Dellborg, Mikael
    Ekman, Inger
    Committed to Life: Adolescents' and Young Adults' Experiences of Living with Fontan Circulation2015Ingår i: Congenital Heart Disease, ISSN 1747-079X, E-ISSN 1747-0803, Vol. 10, nr 5, s. 403-412Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Single ventricle defects are among the most complex congenital heart defects and the development of advanced surgical procedures in recent decades has created the first generation of adolescents and young adults living with this condition. Yet little is known about how these individuals experience life and what impact the heart defect has on their life in general. Objective: The aim was to illuminate and gain a deeper understanding of adolescents' and young adults' experiences of living with a surgically palliated univentricular heart. Design: Seven open-ended in-depth interviews were conducted, transcribed, and analyzed according to the henomenological hermeneutical method. All adolescents and young adults operated before 1995 according to the Fontan procedure or the total cavo-pulmonary connection procedure at one pediatric cardiology unit were included in the study. They were 17-32 years of age (median age 22 years). Results: The interpretation of the interview transcripts showed that the participants experienced living with a surgically palliated univentricular heart in terms of feeling exceptional, strong, and healthy. This was supported by two structural analyses, where three themes emerged: happiness over being me, focusing on possibilities, and being committed to life. Conclusion: Living with a Fontan circulation included negative experiences but the analyses clearly demonstrated a feeling of being strong and healthy. An appreciation of having survived and being committed to life was found to be an integral part of the development of the interviewees' existential growth. This probably strengthens them further in their ability to balance expectations and hurdles in life. This study provides valuable insights into the experience of patients after the Fontan procedure and the importance of a positive health care environment throughout their lives.

  • 13.
    Birkeland, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Dahlgren, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen.
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Breaking bad news: an interview study of paediatric cardiologists2011Ingår i: Cardiology in the Young, ISSN 1047-9511, E-ISSN 1467-1107, Vol. 21, nr 3, s. 286-291Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Technical developments in paediatric cardiology over the last few decades have increased expectations on professionals, demanding of them more emotional competence and communicative ability. The aim of this study was to examine the approach of paediatric cardiologists in informing and communicating with the family of the patient.

    Method: A qualitative interview method was first tested in a pilot study with two paediatric cardiologists. There were nine subsequent semi-structured interviews that were carried out with paediatric cardiologists. A researcher performed all the interviews, which were taped, transcribed, decoded, and analysed.

    Results: Among paediatric cardiologists, how to break bad news to the family is an important concern, evident in findings regarding the significance of trust and confidence, the use of different emotional positions, and a common ambition to achieve skills to handle the situation. There is a need for reflection, education, and sharing of experiences. The cardiologists desire further development of teamwork and of skills in medical students and residents for delivering bad news.

    Conclusions: Doctors are expected to cope with the complexities of diagnoses and decisions, while simultaneously being sensitive to the feelings of the parents, aware of their own emotions, and able to keep it all under control in the context of breaking the bad news to the parents and keeping them informed. These conflicting demands create a need to expand the professional role of the doctor by including more training in emotional competence and communicative ability, beginning in medical school and continuing through consultancy.

  • 14.
    Birkeland, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hagglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Dahlgren, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Interprofessional teamwork in Swedish pediatric cardiology: a national exploratory study2013Ingår i: Journal of Interprofessional Care, ISSN 1356-1820, E-ISSN 1469-9567, Vol. 27, nr 4, s. 320-325Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    This paper aims to describe the nature of pediatric cardiology teams (PCTs) based in Sweden through the use of a mixed methods approach. Questionnaires examining issues about the organization/ways of working, functions/tasks and attitudes were answered by 30 PCTs. Focus group interviews were conducted with six PCTs, selected purposefully by size and location, and information on experiences and attitudes on interprofessional teamwork was explored in depth. Results from the quantitative indicated that in 17 of the teams, where the nurse acted as the central coordinator, there was a positive attitude to the value of teamwork. In the interviews, different problems and needs of improvements were mentioned regarding structure, leadership, presence of physicians in the team as well as the team's mandate. All of the participants, however, agreed that interprofessional teams were required to manage the complexity of the children's care. In conclusion, this study suggests that PCTs need further support to develop structure, leadership and coordination of resources to function in a more effective manner. National plans or recommendations that mandate the organization and working methods of PCTs would be helpful for the ongoing development of PCTs in Sweden.

  • 15.
    Birkeland, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hällgren Graneheim, Ulla
    Umeå universitet, Medicinska fakulteten, Institutionen för omvårdnad.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Dahlgren, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen.
    Facing bad news: a case study focusing on families having a child with congenital heart diseaseManuskript (preprint) (Övrigt vetenskapligt)
  • 16.
    Birkeland, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Dahlgren, Lars
    Umeå universitet, Samhällsvetenskapliga fakulteten, Sociologiska institutionen.
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    Teamwork in Swedish paediatric cardiology: a national exploratory study examining function and dynamicsManuskript (preprint) (Övrigt vetenskapligt)
  • 17.
    Birkeland, Anna-Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hägglöf, Bruno
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Barn- och ungdomspsykiatri.
    The complexity of the psychosocial situation in children and adolescents with heart disease2005Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 94, nr 10, s. 1495-1501Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: To describe the psychosocial situation of children/adolescents with heart disease and their families, an inventory method was worked out.

    Methods: Ninety-seven children/adolescents with congenital heart disease (CHD) were graded into three categories with respect to complexity of CHD. Group I included 42 patients with malformations requiring standardized operations. Group II included 20 patients with more complicated malformations, and group III included 35 patients with very complex malformations. The patients were compared with controls without heart disease, matched for age and gender. The psychosocial impact of CHD was measured by the inventory.

    Results: The most frequent problems in the patient group were healthcare and treatment-related needs (71/97) in the external sphere, family symptoms (68/97) in the interpersonal sphere, and somatic symptoms (19/97) in the personal sphere. Corresponding numbers in the controls were treatment-related needs (15/97), family (9/97) and somatic symptoms (25/97). Fifty per cent of the symptoms in the patient groups were mild, 30% moderate and 20% severe. The most severe symptoms were found in the interpersonal sphere, where family symptoms constituted the most severe variable. The frequency of severe problems in the personal sphere was 11% in the patients and 1% in the controls. This inventory method differentiates the grades of medical complexity both regarding number and severity of psychosocial symptoms. It indicates severe personal problems in the most complex group and shows that they have severe personal problems independent of family problems.

    Conclusion: This study elucidates the psychosocial complexity in children/adolescents with CHD, which has clinical implications in developing a psychosocial care programme.

  • 18. Bratt, E. L.
    et al.
    Burström, Å.
    Hanseus, K.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Berghammer, M.
    Do not forget the parents: Parents' concerns during transition to adult care for adolescents with congenital heart disease2018Ingår i: Child Care Health and Development, ISSN 0305-1862, E-ISSN 1365-2214, Vol. 44, nr 2, s. 278-284Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Growing up with congenital heart disease (CHD) often means transfer to adult care and lifelong medical follow-up. An optimal transition process usually involves a multipart collaboration between the patient, their parents and other family members, and the healthcare providers. Taking an active role while knowing when it is time to step aside can be difficult for all the concerned parties, even the healthcare professionals. The aim of the present study therefore, was to explore parents' expectations and needs during their adolescent's transition to adult care.

    Method: Semi-structured interviews were conducted with 18 parents of 16 adolescents (aged 13-18years) with CHD in 4 pediatric cardiology settings in Sweden. The interviews were analysed with qualitative content analysis.

    Results: The analysis resulted in 2 main themes: (a) Feeling securethe importance of being prepared and informed. This theme focused on the need to be prepared and informed about transition and future transfer to adult care. (b) Recognizing when to hand over at the right time. This theme addressed the process of handing over the responsibility from the parent to the adolescents and contained handing over from pediatric care to adult care.

    Conclusion: Being prepared and informed about the upcoming transition process was essential. The parents underlined the importance of being involved in the transition planning for gradually handing over responsibility to the adolescent. They also considered establishing contact with the adult healthcare team before transfer as important and needed to be assured that CHD-related information of importance for the young person's daily life would be given.

  • 19.
    Bratt, Ewa-Lena
    et al.
    Institute of Health and Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Västra Götaland, Sahlgrenska University Hospital, Children's Heart Center, Gothenburg, Sweden.
    Mora, Mariela Acuna
    Institute of Health and Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Academy of Caring Science, Work Life and Social Welfare, University of Borås, Sweden.
    Sparud-Lundin, Carina
    Institute of Health and Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Saarijärvi, Markus
    Institute of Health and Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Learning, Informatics, Management and Ethics, Medical Management Centre, Karolinska Institutet, Stockholm, Sweden.
    Burström, Åsa
    Department of Neurobiology, Care Sciences and Society Karolinska Institutet, Stockholm, Sweden.
    Skogby, Sandra
    Institute of Health and Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Department of Paediatric Cardiology, The Queen Silvia Children's Hospital, Gothenburg, Sweden.
    Fernlund, Eva
    Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden; Division of Paediatrics, Crown Princess Victoria Childreńs Hospital, Linköping University Hospital, Linköping, Sweden; Department of Clinical Sciences Lund, Lund University, Skåne University Hospital, paediatric Cardiology, Lund, Sweden.
    Fadl, Shalan
    Department of Paediatrics, Örebro University Hospital, Örebro, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap.
    Hanseus, Katarina
    Children's Heart Centre, Skåne University Hospital Lund, Lund, Sweden.
    Kazamia, Kalliopi
    Children's Heart Centre Stockholm-Uppsala, Karolinska University Hospital and Akademiska University Hospital, Sweden; Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
    Moons, Philip
    Institute of Health and Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; KU Leuven, Department of Public Health and Primary Care, Leuven, Belgium; Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
    Effectiveness of the STEPSTONES transition program for adolescents with congenital heart disease: a randomized controlled trial2023Ingår i: Journal of Adolescent Health, ISSN 1054-139X, E-ISSN 1879-1972, Vol. 73, nr 4, s. 655-663Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Purpose: Adolescents with congenital heart disease transition from childhood to adulthood and transfer from pediatric-oriented to adult-oriented care. High-level empirical evidence on the effectiveness of transitional care is scarce. This study investigated the empowering effect (primary outcome) of a structured person-centered transition program for adolescents with congenital heart disease and studied its effectiveness on transition readiness, patient-reported health, quality of life, health behaviors, disease-related knowledge, and parental outcomes e.g., parental uncertainty, readiness for transition as perceived by the parents (secondary outcomes).

    Methods: The STEPSTONES-trial comprised a hybrid experimental design whereby a randomized controlled trial was embedded in a longitudinal observational study. The trial was conducted in seven centers in Sweden. Two centers were allocated to the randomized controlled trial-arm, randomizing participants to intervention or control group. The other five centers were intervention-naïve centers and served as contamination check control group. Outcomes were measured at the age of 16 years (baseline), 17 years, and 18.5 years.

    Results: The change in empowerment from 16 years to 18.5 years differed significantly between the intervention group and control group (mean difference = 3.44; 95% confidence interval = 0.27–6.65; p = .036) in favor of intervention group. For the secondary outcomes, significant differences in change over time were found in parental involvement (p = .008), disease-related knowledge (p = .0002), and satisfaction with physical appearance (p = .039). No differences in primary or secondary outcomes were detected between the control group and contamination check control group, indicating that there was no contamination in the control group.

    Discussion: The STEPSTONES transition program was effective in increasing patient empowerment, reducing parental involvement, improving satisfaction with physical appearance, and increasing disease-related knowledge.

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  • 20. Burström, Åsa
    et al.
    Bratt, Ewa-Lena
    Frenckner, Björn
    Nisell, Margret
    Hanséus, Katarina
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Öjmyr-Joelsson, Maria
    Adolescents with congenital heart disease: their opinions about the preparation for transfer to adult care2017Ingår i: European Journal of Pediatrics, ISSN 0340-6199, E-ISSN 1432-1076, Vol. 176, nr 7, s. 881-889Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    The aim of the study was to explore what adolescents with congenital heart disease (CHD) view as important in the preparation for the transfer to adult care. We performed interviews in four focus groups with adolescents (14-18 years old) at four university hospitals in Sweden. Data was analysed using qualitative content analysis. The analysis revealed one main category; Becoming a manager of the condition and four subcategories; Sufficient knowledge about the health, Be a participant in the care, Parental support, and Communicate with others about the health. The adolescents' ages differentiated the discussion in the groups. The older adolescents seemed to have more interest in transition planning, information and transfer. The younger described more frustrations about communication and handling the disease. Conclusion: To become a manager of the CHD in daily life, the adolescents want disease specific knowledge, which should be communicated in a developmentally appropriate way. Adolescents want to participate and be involved in the transition process. They need support and guidance in how to communicate their CHD. Parental support is fundamental but it change over time. Moreover, peer-support is becoming more significant during the transition process.

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  • 21. Burström, Åsa
    et al.
    Mora, Mariela Acuna
    Öjmyr-Joelsson, Maria
    Sparud-Lundin, Carina
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hanseus, Katarina
    Frenckner, Björn
    Nisell, Margret
    Moons, Philip
    Bratt, Ewa-Lena
    Parental uncertainty about transferring their adolescent with congenital heart disease to adult care2019Ingår i: Journal of Advanced Nursing, ISSN 0309-2402, E-ISSN 1365-2648, Vol. 75, nr 2, s. 380-387Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aims: To study parent's levels of uncertainty related to the transfer from pediatric to adult care in adolescents with congenital heart disease (CHD) and to identify potentially correlating factors. Background: Parents acknowledge that during transition they struggle with finding ways of feeling secure in handing over the responsibility and letting go of control. Well-prepared and informed parents who feel secure are most likely better skilled to support their adolescent and to hand over the responsibility. Design: A cross-sectional study. Methods: Overall, 351 parents were included (35% response rate). Parental uncertainty was assessed using a Linear Analogue Scale (0-100). Data were collected between January - August 2016. Potential correlates were assessed using the readiness for transition questionnaire and sociodemographic data. Results: The mean parental uncertainty score was 42.5. Twenty-four percent of the parents had a very low level of uncertainty (score 0-10) and 7% had a very high level (score 91-100). Overall, 26% of the mothers and 36% of the fathers indicated that they had not started thinking of the transfer yet. The level of uncertainty was negatively associated with the level of perceived overall readiness. Adolescents' age, sex, CHD complexity, and parental age were not related to uncertainty. Conclusion: A wide range in the levels of uncertainty was found. Parents who were less involved in the care, or perceived their adolescent as readier for the transition, felt less uncertain. Still, thirty percent of the parents had not started to think about the transfer to adult care.

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  • 22. Burström, Åsa
    et al.
    Mora, Mariela Acuna
    Öjmyr-Joelsson, Maria
    Sparud-Lundin, Carina
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Hanseus, Katarina
    Frenckner, Björn
    Nisell, Margret
    Moons, Philip
    Bratt, Ewa-Lena
    Ready for Transfer to Adult Care?: A Triadic Evaluation of Transition Readiness in Adolescents With Congenital Heart Disease and Their Parents2019Ingår i: Journal of Family Nursing, ISSN 1074-8407, E-ISSN 1552-549X, Vol. 25, nr 3, s. 447-468, artikel-id 1074840719864255Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Transfer to adult care for adolescents with chronic conditions ought to be determined by transition readiness. The aims of this study were (a) to describe the level of readiness for transition in adolescents with congenital heart disease, (b) to compare adolescents' assessment of transition readiness with their parents' assessments, and (c) to study potential correlates of transition readiness. A total of 157 triads of adolescents aged 14 to 18 years and their parents completed the Readiness for Transition Questionnaire. Adolescents scored higher on overall readiness than their parents. Multivariable analyses revealed that higher levels of adolescents' overall readiness were associated with a less threatening view of the illness, a higher level of empowerment, and with higher mothers' and fathers' overall readiness scores. Adolescents' responsibility scores were positively associated with age and parental adolescent responsibility scores. Parental involvement scores were negatively associated with adolescents' age and positively with the mothers' parental involvement scores. By using a triadic evaluation, the results of the present study significantly extend what is currently known about this population.

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  • 23.
    Charisopoulou, Dafni
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Division of Pediatric Cardiology, Department of Pediatrics, Amalia Children’s Hospital, Radboud University Medical Center, 6500 HB Nijmegen, The Netherlands; Academic Centre for Congenital Heart Disease, 6500 HB Nijmegen, The Netherlands.
    Koulaouzidis, George
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Law, Lucy
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Exercise Induced Worsening of Mechanical Heterogeneity and Diastolic Impairment in Long QT Syndrome2021Ingår i: Journal of Clinical Medicine, E-ISSN 2077-0383, Vol. 10, nr 1, s. 1-12, artikel-id 37Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Electromechanical heterogeneities due to marked dispersion of ventricular repolarisation and mechanical function have been associated with symptoms in long QT syndrome (LQTS) patients.

    Aim: To examine the exercise response of longitudinal LV systolic and diastolic myocardial function and synchronicity in LQTS patients and its relationship with symptoms; Methods: Forty seven (age 45 ± 15 yrs, 25 female, 20 symptomatic) LQTS patients and 35 healthy individuals underwent an exercise test (Bruce protocol). ECG and echo parameters were recorded at rest, peak exercise (p.e.), and recovery.

    Results: LQTS patients had prolonged and markedly dispersed myocardial contraction, delayed early relaxation phase, and significantly decreased filling time at all exercise phases. Unlike controls, these electromechanical disturbances deteriorated further with exercise, during which additional decrease of the LV diastolic myocardial function and attenuated LV stroke volume were noted. Such abnormal responses to exercise were seen to a greater degree in symptomatic patients and in the LQT1 subgroup and improved with B-blocker therapy. Worsening myocardial contraction dispersion at p.e. was the strongest discriminator for previous clinical events, and its discriminating power excelled further by adding early relaxation delay.

    Conclusions: Electromechanical disturbances were shown to worsen during exercise in LQTS patients and were more pronounced in those with previous arrhythmic events.

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  • 24.
    Charisopoulou, Dafni
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Paediatric Cardiology, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
    Koulaouzidis, George
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Department of Cardiology, Mid Yorkshire Hospitals NHS Trust, Wakefield, UK.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Henein, Michael
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Molecular and Clinical Sciences Research Institute, St George University London, London, UK; Brunel University, Middlesex, UK.
    Exercise worsening of electromechanical disturbances: a predictor of arrhythmia in long QT syndrome2019Ingår i: Clinical Cardiology, ISSN 0160-9289, E-ISSN 1932-8737, Vol. 42, nr 2, s. 235-240Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background; Electromechanical (EM) coupling heterogeneity is significant in long QT syndrome (LQTS), particularly in symptomatic patients; EM window (EMW) has been proposed as an indicator of interaction and a better predictor of arrhythmia than QTc. Hypothesis To investigate the dynamic response of EMW to exercise in LQTS and its predictive value of arrhythmia.

    Methods: Forty-seven LQTS carriers (45 +/- 15 years, 20 with arrhythmic events), and 35 controls underwent exercise echocardiogram. EMW was measured as the time difference between aortic valve closure on Doppler and the end of QT interval on the superimposed electrocardiogram (ECG). Measurements were obtained at rest, peak exercise (PE) and 4 minutes into recovery.

    Results: Patients did not differ in age, gender, heart rate, or left ventricular ejection fraction but had a negative resting EMW compared with controls (-42 +/- 22 vs 17 +/- 5 ms, P < 0.0001). EMW became more negative at PE (-89 +/- 43 vs 16 +/- 7 ms, P = 0.0001) and recovery (-65 +/- 39 vs 16 +/- 6 ms, P = 0.001) in patients, particularly the symptomatic, but remained unchanged in controls. PE EMW was a stronger predictor of arrhythmic events than QTc (AUC:0.765 vs 0.569, P < 0.001). B-blockers did not affect EMW at rest but was less negative at PE (BB: -66 +/- 21 vs no-BB: -113 +/- 25 ms, P < 0.001). LQT1 patients had worse PE EMW negativity than LQT2.

    Conclusion: LQTS patients have significantly negative EMW, which worsens with exercise. These changes are more pronounced in patients with documented arrhythmic events and decrease with B-blocker therapy. Thus, EMW assessment during exercise may help improve risk stratification and management of LQTS patients.

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  • 25.
    Charisopoulou, Dafni
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Department of Paediatric Cardiology, Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK.
    Koulaouzidis, George
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi. Molecular & Clinical Sciences Research Institute, St George University, London, UK.
    Abnormal ventricular repolarization in long QT syndrome carriers is related to short left ventricular filling time and attenuated stroke volume response during exercise2018Ingår i: Echocardiography, ISSN 0742-2822, E-ISSN 1540-8175, Vol. 35, nr 8, s. 1116-1123Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Long QT syndrome (LQTS) carriers are characterized by abnormal ventricular repolarization, prolonged systole, and mechanical dispersion. Prolonged left ventricular (LV) systole has been shown to result in disproportionate shortening of LV filling in other conditions. The aim of this study was to assess LV filling, diastolic function, and stroke volume (SV) response to dynamic exercise, in a group of LQTS carriers.

    METHODS: Forty-seven LQTS carriers (45 ± 15 years, 20 symptomatic) and 35 healthy individuals underwent bicycle stress echocardiogram. Electrocardiographic and echocardiographic measurements were obtained at rest, peak exercise, and 4 minutes into recovery.

    RESULTS: Long QT syndrome carriers and controls did not differ in age, gender, heart rate, QRS duration, or LV ejection fraction. At rest, LQTS carriers had longer QTc and shorter filling time (FT). At peak exercise, QTc increased and remained longer than controls at recovery. A negative correlation was found between QTc and FT (r = -.398, P = .001) with greater fall in FT in LQTS carriers than in controls at peak exercise (-23% ± 10 vs +2% ± 3, P < .0001). FT correlated with SV (r = +.27, P = .001), which increased more in controls than in LQTS carriers (+32% ± 4 vs +2% ± 1, P < .05). These differences were more pronounced in symptomatic LQTS carriers who had shorter FT and smaller SV at peak exercise and during recovery compared to asymptomatics (P < .05).

    CONCLUSIONS: Long QT syndrome carriers have longer QTc, but also shorter FT. These disturbances worsen at peak exercise (particularly in symptomatics) compromising LV filling and SV, hence a potential pathomechanism for adverse events.

  • 26.
    Charisopoulou, Dafni
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin. Division of Pediatric Cardiology, Department of Pediatrics, Amalia Children’s Hospital, Radboud University Medical Center, Nijmegen, Netherlands; Academic Centre for Congenital Heart Disease, Nijmegen, Netherlands.
    Koulaouzidis, George
    Department of Biochemical Sciences, Pomeranian Medical University, Szczecin, Poland.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Reversed Apico-Basal Myocardial Relaxation Sequence During Exercise in Long QT Syndrome Mutations Carriers With History of Previous Cardiac Events2022Ingår i: Frontiers in Physiology, E-ISSN 1664-042X, Vol. 12, artikel-id 780448Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Recent echocardiography studies in inherited long QT syndrome (LQTS) have shown left ventricular (LV) myocardial relaxation disturbances to follow markedly prolonged and dispersed mechanical contraction. Aim: We used speckle-tracking echocardiography to assess disturbances in LV myocardial relaxation sequence during exercise and their relationship to symptoms. Methods: Forty seven LQTS patients (45 ± 15 years, 25 female and 20 symptomatic, LVEF: 65 ± 6%) and 35 controls underwent exercise echocardiogram using Bruce protocol. ECG and echo parameters were recorded at rest, peak exercise (p.e.) and recovery. Results: Between patients and controls there were no differences in age, gender, HR or LVEF. At p.e, patients had longer time to LV longitudinal ESR (tESR) at all three LV segments; basal (p < 0.0001), mid- cavity (p = 0.03) and apical (p = 0.03) whereas at rest such difference was noted only at base (p = 0.0007). Patients showed reversed apico-basal relaxation sequence (ΔtESRbase–apex) with early relaxation onset occurring later at base than at apex, both at rest (49 ± 43 vs. –29 ± 19 ms, p < 0.0001) and at p.e. (46 ± 38 vs. –40 ± 22 ms, p < 0.0001), particularly in symptomatic patients (69 ± 44 vs. 32 ± 26, p < 0.0007). ΔtESRbase–apex correlated with longer QTc interval, lower ESR and attenuated LV stroke volume. Conclusion: LQTS patients show reversed longitudinal relaxation sequence, which worsens with exercise, particularly in those with previous cardiac events.

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  • 27. Chockalingam, Priya
    et al.
    Crotti, Lia
    Girardengo, Giulia
    Johnson, Jonathan N
    Harris, Katy M
    van der Heijden, Jeroen F
    Hauer, Richard NW
    Beckmann, Britt M
    Spazzolini, Carla
    Rordorf, Roberto
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Clur, Sally-Ann B
    Fischer, Markus
    van den Heuvel, Freek
    Kaeaeb, Stefan
    Blom, Nico A
    Ackerman, Michael J
    Schwartz, Peter J
    Wilde, Arthur AM
    Not all beta-blockers are equal in the management of Long QT Syndrome types 1 and 2: higher recurrence of events under metoprolol2012Ingår i: Journal of the American College of Cardiology, ISSN 0735-1097, E-ISSN 1558-3597, Vol. 60, nr 20, s. 2092-2099Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Objectives The purpose of this study was to compare the efficacy of beta-blockers in congenital long QT syndrome (LQTS). Background Beta-blockers are the mainstay in managing LQTS. Studies comparing the efficacy of commonly used beta-blockers are lacking, and clinicians generally assume they are equally effective.

    Methods Electrocardiographic and clinical parameters of 382 LQT1/LQT2 patients initiated on propranolol (n = 134), metoprolol (n = 147), and nadolol (n = 101) were analyzed, excluding patients <1 year of age at beta-blocker initiation. Symptoms before therapy and the first breakthrough cardiac events (BCEs) were documented.

    Results Patients (56% female, 27% symptomatic, heart rate 76 +/- 16 beats/min, QTc 472 +/- 46 ms) were started on beta-blocker therapy at a median age of 14 years (interquartile range: 8 to 32 years). The QTc shortening with propranolol was significantly greater than with other beta-blockers in the total cohort and in the subset with QTc >480 ms. None of the asymptomatic patients had BCEs. Among symptomatic patients (n = 101), 15 had BCEs (all syncopes). The QTc shortening was significantly less pronounced among patients with BCEs. There was a greater risk of BCEs for symptomatic patients initiated on metoprolol compared to users of the other 2 beta-blockers combined, after adjustment for genotype (odds ratio: 3.95, 95% confidence interval: 1.2 to 13.1, p = 0.025). Kaplan-Meier analysis showed a significantly lower event-free survival for symptomatic patients receiving metoprolol compared to propranolol/nadolol.

    Conclusions Propranolol has a significantly better QTc shortening effect compared to metoprolol and nadolol, especially in patients with prolonged QTc. Propranolol and nadolol are equally effective, whereas symptomatic patients started on metoprolol are at a significantly higher risk for BCEs. Metoprolol should not be used for symptomatic LQT1 and LQT2 patients.

    (J Am Coll Cardiol 2012;60:2092-9) (C) 2012 by the American College of Cardiology Foundation

  • 28. Clur, Sally-Ann B
    et al.
    Vink, Arja S
    Etheridge, Susan P
    Robles de Medina, Pascale G
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Ackerman, Michael J
    Wilde, Arthur A
    Blom, Nico A
    Benson, D Woodrow
    Herberg, Ulrike
    Donofrio, Mary T
    Cuneo, Bettina F
    Left Ventricular Isovolumetric Relaxation Time Is Prolonged in Fetal Long-QT Syndrome2018Ingår i: Circulation: Arrhythmia and Electrophysiology, ISSN 1941-3149, E-ISSN 1941-3084, Vol. 11, nr 4, artikel-id e005797Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Long-QT syndrome (LQTS), an inherited cardiac repolarization disorder, is an important cause of fetal and neonatal mortality. Detecting LQTS prenatally is challenging. A fetal heart rate (FHR) less than third percentile for gestational age is specific for LQTS, but the sensitivity is only ≈50%. Left ventricular isovolumetric relaxation time (LVIRT) was evaluated as a potential diagnostic marker for fetal LQTS.

    METHODS AND RESULTS: <0.001), as was the N-LVIRT. The best cutoff to diagnose LQTS was N-LVIRT ≥11.3 at ≤20 weeks (92% sensitivity, 70% specificity). Simultaneous analysis of N-LVIRT and FHR improved the sensitivity and specificity for LQTS (area under the curve=0.96; 95% confidence interval, 0.82-1.00 at 21-30 weeks). N-LVIRT, LV myocardial performance index, and FHR trends differed significantly between LQTS fetuses and controls through gestation.

    CONCLUSIONS: The LVIRT is prolonged in LQTS fetuses. Findings of a prolonged N-LVIRT and sinus bradycardia can improve the prenatal detection of fetal LQTS.

  • 29. Cuneo, Bettina F.
    et al.
    Kaizer, Alexander M.
    Clur, Sally Ann
    Swan, Heikki
    Herberg, Ulrike
    Winbo, Annika
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Haugaa, Kristina
    Etheridge, Susan
    Ackerman, Michael J.
    Dagradi, Federica
    Killen, Stacy A. S.
    Wacker-Gussmann, Annette
    Benson, D. Woodrow
    Wilde, A. A. M.
    Pan, Zhaoxing
    Lam, Aimee
    Spazzolini, Carla
    Horigome, Hitoshi
    Schwartz, Peter J.
    Mothers with long QT syndrome are at increased risk for fetal death: findings from a multicenter international study2020Ingår i: American Journal of Obstetrics and Gynecology, ISSN 0002-9378, E-ISSN 1097-6868, Vol. 222, nr 3, s. 1-11, artikel-id 263.e1-11Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Most fetal deaths are unexplained. Long QT syndrome is a genetic disorder of cardiac ion channels. Affected individuals, including fetuses, are predisposed to sudden death. We sought to determine the risk of fetal death in familial long QT syndrome, in which the mother or father carries the long QT syndrome genotype. In addition, we assessed whether risk differed if the long QT syndrome genotype was inherited from the mother or father. OBJECTIVE: This was a retrospective review of pregnancies in families with the 3 most common heterozygous pathogenic long QT syndrome genotypes in KCNQ1 (LQT1), KCNH2 (LQT2), or SCN5A (LQT3), which occur in approximately 1 in 2000 individuals. The purpose of our study was to compare pregnancy and birth outcomes in familial long QT syndrome with the normal population and between maternal and paternal carriers of the long QT syndrome genotype. We hypothesized that fetal death before (miscarriage) and after (stillbirths) 20 weeks gestation would be increased in familial long QT syndrome compared with the normal population and that the parent of origin would not affect birth outcomes. STUDY DESIGN: Our study was a multicenter observational case series of 148 pregnancies from 103 families (80 mothers, 23 fathers) with familial long QT syndrome (60 with LQT1, 29 with LQT2, 14 with LQT3) who were recruited from 11 international centers with expertise in hereditary heart rhythm diseases, pediatric and/or adult electrophysiology, and high-risk pregnancies. Clinical data-bases from these sites were reviewed for long QT syndrome that occurred in men or women of childbearing age (18-40 years). Pregnancy outcomes (livebirth, stillbirth, and miscarriage), birthweights, and gestational age at delivery were compared among long QT syndrome genotypes and between maternal vs paternal long QT syndrome-affected status with the use of logistic regression analysis. RESULTS: Most offspring (80%; 118/148) were liveborn at term; 66% of offspring (73/110) had long QT syndrome. Newborn infants of mothers with long QT syndrome were delivered earlier and, when the data were controlled for gestational age, weighed less than newborn infants of long QT syndrome fathers. Fetal arrhythmias were observed rarely, but stillbirths (fetal death at >20 weeks gestation) were 8 times more frequent in long QT syndrome (4% vs approximately 0.5%); miscarriages (fetal death at <= 20 weeks gestation) were 2 times that of the general population (16% vs 8%). The likelihood of fetal death was significantly greater with maternal vs paternal long QT syndrome (24.4% vs 3.4%; P = .036). Only 10% of all fetal deaths underwent postmortem long QT syndrome testing; 2 of 3 cases were positive for the family long QT syndrome genotype. CONCLUSION: This is the first report to demonstrate that mothers with long QT syndrome are at increased risk of fetal death and to uncover a previously unreported cause of stillbirth. Our results suggest that maternal effects of long QT syndrome channelopathy may cause placental or myometrial dysfunction that confers increased susceptibility to fetal death and growth restriction in newborn survivors, regardless of long QT syndrome status.

  • 30.
    Dahlberg, Pia
    et al.
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Vaestra Goetaland, Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Axelsson, Karl-Jonas
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Vaestra Goetaland, Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lundahl, Gunilla
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Gransberg, Lennart
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Bergfeldt, Lennart
    Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Region Vaestra Goetaland, Department of Cardiology, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Spatiotemporal repolarization dispersion before and after exercise in patients with long QT syndrome type 1 versus controls: probing into the arrhythmia substrate2023Ingår i: American Journal of Physiology. Heart and Circulatory Physiology, ISSN 0363-6135, E-ISSN 1522-1539, Vol. 325, nr 6, s. H1279-H1289Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Congenital long QT syndrome (LQTS) carries an increased risk for syncope and sudden death. QT prolongation promotes ventricular extrasystoles, which, in the presence of an arrhythmia substrate, might trigger ventricular tachycardia degenerating into fibrillation. Increased electrical heterogeneity (dispersion) is the suggested arrhythmia substrate in LQTS. In the most common subtype LQT1, physical exercise predisposes for arrhythmia and spatiotemporal dispersion was therefore studied in this context. Thirty-seven patients (57% on β-blockers) and 37 healthy controls (mean age, 31 vs. 35; range, 6-68 vs. 6-72 yr) performed an exercise test. Frank vectorcardiography was used to assess spatiotemporal dispersion as Tampl, Tarea, the ventricular gradient (VG), and the Tpeak-end interval from 10-s signal averages before and 7 ± 2 min after exercise; during exercise too much signal disturbance excluded analysis. Baseline and maximum heart rates as well as estimated exercise intensity were similar, but heart rate recovery was slower in patients. At baseline, QT and heart rate-corrected QT (QTcB) were significantly longer in patients (as expected), whereas dispersion parameters were numerically larger in controls. After exercise, QTpeakcB and Tpeak-endcB increased significantly more in patients (18 ± 23 vs. 7 ± 10 ms and 12 ± 17 vs. 2 ± 6 ms; P < 0.001 and P < 0.01). There was, however, no difference in the change in Tampl, Tarea, and VG between groups. In conclusion, although temporal dispersion of repolarization increased significantly more after exercise in patients with LQT1, there were no signs of exercise-induced increase in global dispersion of action potential duration and morphology. The arrhythmia substrate/mechanism in LQT1 warrants further study.

    NEW & NOTEWORTHY: Physical activity increases the risk for life-threatening arrhythmias in LQTS type 1 (LQT1). The arrhythmia substrate is presumably altered electrical heterogeneity (a.k.a. dispersion). Spatiotemporal dispersion parameters were therefore compared before and after exercise in patients versus healthy controls using Frank vectorcardiography, a novelty. Physical exercise prolonged the time between the earliest and latest complete repolarization in patients versus controls, but did not increase parameters reflecting global dispersion of action potential duration and morphology, another novelty.

  • 31. Dahlberg, Pia
    et al.
    Diamant, Ulla-Britt
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Gilljam, Thomas
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Bergfeldt, Lennart
    QT correction using Bazett's formula remains preferable in long QT syndrome type 1 and 22021Ingår i: Annals of Noninvasive Electrocardiology, ISSN 1082-720X, E-ISSN 1542-474X, Vol. 26, nr 1, artikel-id e12804Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: The heart rate (HR) corrected QT interval (QTc) is crucial for diagnosis and risk stratification in the long QT syndrome (LQTS). Although its use has been questioned in some contexts, Bazett's formula has been applied in most diagnostic and prognostic studies in LQTS patients. However, studies on which formula eliminates the inverse relation between QT and HR are lacking in LQTS patients. We therefore determined which QT correction formula is most appropriate in LQTS patients including the effect of beta blocker therapy and an evaluation of the agreement of the formulae when applying specific QTc limits for diagnostic and prognostic purposes.

    Methods: Automated measurements from routine 12-lead ECGs from 200 genetically confirmed LQTS patients from two Swedish regions were included (167 LQT1, 33 LQT2). QT correction was performed using the Bazett, Framingham, Fridericia, and Hodges formulae. Linear regression was used to compare the formulae in all patients, and before and after the initiation of beta blocking therapy in a subgroup (n = 44). Concordance analysis was performed for QTc >= 480 ms (diagnosis) and >= 500 ms (prognosis).

    Results: The median age was 32 years (range 0.1-78), 123 (62%) were female and 52 (26%) were children <= 16 years. Bazett's formula was the only method resulting in a QTc without relation with HR. Initiation of beta blocking therapy did not alter the result. Concordance analyses showed clinically significant differences (Cohen's kappa 0.629-0.469) for diagnosis and prognosis in individual patients.

    Conclusion: Bazett's formula remains preferable for diagnosis and prognosis in LQT1 and 2 patients.

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  • 32.
    Diamant, Ulla-Britt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Vectorcardiographic recordings of the Q-T interval in a pediatric long Q-T syndrome population2013Ingår i: Pediatric Cardiology, ISSN 0172-0643, E-ISSN 1432-1971, Vol. 34, nr 2, s. 245-249Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Measurements of the Q-T interval are less reliable in children than in adults. Identification of superior diagnostic tools is warranted. This study aimed to investigate whether a vectorcardiogram (VCG) recorded from three orthogonal leads (X, Y, Z) according to Frank is superior to a 12-lead electrocardiogram (ECG) in providing a correct long Q-T syndrome (LQTS) diagnosis in children. This LQTS group consisted of 35 genetically confirmed carriers of mutations in the KCNQ1 (n = 29) and KCNH2 (n = 6) genes. The control group consisted of 35 age- and gender-matched healthy children. The mean age was 7 years in the LQTS group and 6.7 years in the control group (range, 0.5-16 years). The corrected Q-T interval (QT(c)) was measured manually (QT(man)) by one author (A.W.). The 12-lead ECG automatic measurements (QT(ECG)) and interpretation (QT(Interpret)) of QT(c) were performed with the Mac5000 (GE Medical System), and the VCG automatic measurements (QT(VCG)) were performed with the Mida1000, CoroNet (Ortivus AB, Sweden). By either method, a QT(c) longer than 440 ms was considered prolonged and indicative of LQTS. Of the 35 children with genetically confirmed LQTS, 30 (86 %) received a correct diagnosis using QT(VCG), 29 (82 %) using QT(man), 24 (69 %) using QT(ECG), and 17 (49 %) using QT(Interpret). Specificity was 0.80 for QT(VCG), 0.83 for QT(man), 0.77 for QT(ECG), and 0.83 for QT(Interpret). The VCG automatic measurement of QT(c) seems to be a better predictor of LQTS than automatic measurement and interpretation of 12-lead ECG.

  • 33.
    Diamant, Ulla-Britt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Vahedi, Farzad
    Sahlgrenska Akademin Göteborgs Universitet.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bergfeldt, Lennart
    Sahlgrenska Akademin Göteborgs Universitet.
    Electrophysiological phenotype in the LQTS mutations Y111C and R518X in the KCNQ1 gene2013Ingår i: Journal of applied physiology, ISSN 8750-7587, E-ISSN 1522-1601, Vol. 115, nr 10, s. 1423-1432Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Long QT syndrome is the prototypical disorder of ventricular repolarization (VR), and a genotype-phenotype relation is postulated. Furthermore, although increased VR heterogeneity (dispersion) may be important in the arrhythmogenicity in long QT syndrome, this hypothesis has not been evaluated in humans and cannot be tested by conventional electrocardiography. In contrast, vectorcardiography allows assessment of VR heterogeneity and is more sensitive to VR alterations than electrocardiography. Therefore, vectorcardiography was used to compare the electrophysiological phenotypes of two mutations in the LQT1 gene with different in vitro biophysical properties, and with LQT2 mutation carriers and healthy control subjects. We included 99 LQT1 gene mutation carriers (57 Y111C, 42 R518X) and 19 LQT2 gene mutation carriers. Potassium channel function is in vitro most severely impaired in Y111C. The control group consisted of 121 healthy subjects. QRS, QT, and T-peak to T-end (Tp-e) intervals, measures of the QRS vector and T vector and their relationship, and T-loop morphology parameters were compared at rest. Apart from a longer heart rate-corrected QT interval (QT heart rate corrected according to Bazett) in Y111C mutation carriers, there were no significant differences between the two LQT1 mutations. No signs of increased VR heterogeneity were observed among the LQT1 and LQT2 mutation carriers. QT heart rate corrected according to Bazett and Tp-e were longer, and the Tp-e-to-QT ratio greater in LQT2 than in LQT1 and the control group. In conclusion, there was a marked discrepancy between in vitro potassium channel function and in vivo electrophysiological properties in these two LQT1 mutations. Together with previous observations of the relatively low risk for clinical events in Y111C mutation carriers, our results indicate need for cautiousness in predicting in vivo electrophysiological properties and the propensity for clinical events based on in vitro assessment of ion channel function alone.

  • 34.
    Diamant, Ulla-Britt
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap. Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stattin, Eva-Lena
    Umeå universitet, Medicinska fakulteten, Institutionen för medicinsk biovetenskap, Medicinsk och klinisk genetik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Kesek, Milos
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Medicin.
    Two automatic QT algorithms compared with manual measurement in identification of long QT syndrome2010Ingår i: Journal of Electrocardiology, ISSN 0022-0736, E-ISSN 1532-8430, Vol. 43, nr 1, s. 25-30Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Long QT syndrome (LQTS) is an inherited disorder that increases the risk of syncope and malignant ventricular arrhythmias, which may result in sudden death.

    METHODS: We compared manual measurement by 4 observers (QT(manual)) and 3 computerized measurements for QT interval accuracy in the diagnosis of LQTS: 1. QT measured from the vector magnitude calculated from the 3 averaged orthogonal leads X, Y, and Z (QTVCG) and classified using the same predefined QTc cut-points for classification of QT prolongation as in manual measurements; 2. QT measured by a 12-lead electrocardiogram (ECG) program (QTECG) and subsequently classified using the same cut-points as in (1) above; 3. The same QT value as in (2) above, automatically classified by a 12-lead ECG program with thresholds for QT prolongation adjusted for age and sex (QTinterpret). The population consisted of 94 genetically confirmed carriers of KCNQ1 (LQT1) and KCNH2 (LQT2) mutations and a combined control group of 28 genetically confirmed noncarriers and 66 unrelated healthy volunteers.

    RESULTS: QT(VCG) provided the best combination of sensitivity (89%) and specificity (90%) in diagnosing LQTS, with 0.948 as the area under the receiver operating characteristic curve. The evaluation of QT measurement by the 4 observers revealed a high interreader variability, and only 1 of 4 observers showed acceptable level of agreement in LQTS mutation carrier identification (kappa coefficient >0.75).

    CONCLUSION: Automatic QT measurement by the Mida1000/CoroNet system (Ortivus AB, Danderyd, Sweden) is an accurate, efficient, and easily applied method for initial screening for LQTS.

  • 35.
    Fricke, Katrin
    et al.
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden; Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Mellander, Mats
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; Children´s Heart Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Hanséus, Katarina
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden; Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Tran, Phan-Kiet
    Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden; Cardiac Surgery, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden.
    Synnergren, Mats
    Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, Gothenburg, Sweden; Children´s Heart Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Ramgren, Jens Johansson
    Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden; Cardiac Surgery, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sunnegårdh, Jan
    Children´s Heart Centre, Sahlgrenska University Hospital, Gothenburg, Sweden.
    Dalén, Magnus
    Department of Cardiothoracic Surgery, Karolinska University Hospital, Stockholm, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institute, Stockholm, Sweden.
    Sjöberg, Gunnar
    Department of Women’s and Children’s Health, Karolinska Institute, Stockholm, Sweden.
    Weismann, Constance G.
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden.
    Liuba, Petru
    Cardiology, Pediatric Heart Centre, Skåne University Hospital, Lund, Sweden; Pediatrics, Department of Clinical Sciences, Lund University, Lund, Sweden.
    Impact of Left Ventricular Morphology on Adverse Outcomes Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome: 20 Years of National Data From Sweden2022Ingår i: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease, ISSN 2047-9980, E-ISSN 2047-9980, Vol. 11, nr 7, artikel-id e022929Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Hypoplastic left heart syndrome is associated with significant morbidity and mortality. We aimed to assess the influence of left ventricular morphology and choice of shunt on adverse outcome in patients with hypoplastic left heart syndrome and stage 1 palliation.

    METHODS AND RESULTS: This was a retrospective analysis of patients with hypoplastic left heart syndrome with stage 1 palliation between 1999 and 2018 in Sweden. Patients (n=167) were grouped based on the anatomic subtypes aortic-mitral atresia, aortic atresia-mitral stenosis (AA-MS), and aortic-mitral stenosis. The left ventricular phenotypes including globular left ventricle (Glob-LV), miniaturized and slit-like left ventricle (LV), and the incidence of major adverse events (MAEs) including mortality were assessed. The overall mortality and MAEs were 31% and 41%, respectively. AA-MS (35%) was associated with both mortality (all other subtypes versus AA-MS: interstage-I: hazard ratio [HR], 2.7; P=0.006; overall: HR, 2.2; P=0.005) and MAEs (HR, 2.4; P=0.0009). Glob-LV (57%), noticed in all patients with AA-MS, 61% of patients with aortic stenosis-mitral stenosis, and 19% of patients with aortic atresia-mitral atresia, was associated with both mortality (all other left ventricular phenotypes versus Glob-LV: interstage-I: HR, 4.5; P=0.004; overall: HR, 3.4; P=0.0007) and MAEs (HR, 2.7; P=0.0007). There was no difference in mortality and MAEs between patients with AA-MS and without AA-MS with Glob-LV (P>0.15). Patients with AA-MS (35%) or Glob-LV (38%) palliated with a Blalock-Taussig shunt had higher overall mortality compared with those palliated with Sano shunts, irrespective of the stage 1 palliation year (AA-MS: HR, 2.6; P=0.04; Glob-LV: HR, 2.1; P=0.03).

    CONCLUSIONS: Glob-LV and AA-MS are independent morphological risk factors for adverse short-and long-term outcome, especially if a Blalock-Taussig shunt is used as part of stage 1 palliation. These findings are important for the clinical management of patients with hypoplastic left heart syndrome.

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  • 36.
    Grahn, K
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Wikström, S
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Nyman, Linda
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stecksén-Blicks, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Attitudes about dental care among parents whose children suffer from severe congenital heart disease: a case-control study2006Ingår i: International Journal of Paediatric Dentistry, ISSN 0960-7439, E-ISSN 1365-263X, Vol. 16, nr 4, s. 231-238Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    OBJECTIVES: To examine attitudes and experiences of parents whose children have complex congenital heart disease (CHD) with respect to dental health information and advice, dental care, and service and to compare the results with data from an age- and gender-matched control group without any medical problems.

    SETTING: Faculty of Medicine (Paediatric Cardiology and Paediatric Dentistry), Umea University, Umea, Sweden.

    SAMPLE AND METHOD: Each group comprised parents of 33 children; the children's mean age was 9.4 years. All the cases and the controls resided in the county of Vasterbotten, northern Sweden. Data were collected with a questionnaire with 20 joint questions to both groups and four additional questions to the CHD group.

    RESULTS: Of the 20 joint questions, significant differences were displayed in the following areas: the professional group that provided the parents with dental health information and advice (P < 0.01), attitudes to reception at the dental clinic, and experience of sedation before operative dental treatment (P < 0.05). Parents to 11 children with CHD who were patients at a specialist clinic for paediatric dentistry scored the reception at the dental clinic as excellent in nine cases and satisfactory in two, compared to excellent (3), satisfactory (11), decent (4), and poor (4) among those who were patients in general dental practice (P < 0.01). No statistically significant differences in educational level or in parental experience of dental health were noted between the two groups (P > 0.05).

    CONCLUSION: Children with CHD in northern Sweden mainly receive their dental health information from a physician or a dentist, and healthy children mainly receive information from a dental hygienist indicating that children with CHD are given priority in the dental care system. Parental attitudes to reception in the dental service differed, and parents of healthy children scored the reception at the dental clinic better than parents of children with CHD. It is suggested that children with severe CHD should receive dental care in clinics for paediatric dentistry, particularly at early ages.

  • 37. Granberg, Marie
    et al.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fisher, Anne G
    Activities in daily living and schoolwork task performance in children with complex congenital heart disease.2008Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 97, nr 9, s. 1270-4Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIM: To examine if children with complex congenital heart disease (CHD) differ significantly from healthy children in performance of activities in daily living (ADL) and schoolwork tasks. METHODS: Fourteen children with complex CHD (3-14 years) were matched in pairs by age and gender to healthy children (n = 14). The ADL Taxonomy was used to evaluate ability to perform ADL and the School Version of the Assessment of Motor and Process Skills (AMPS) to evaluate quality of schoolwork task performance. RESULTS: The children with complex CHD had significantly lower mean ADL, school motor and school process performance. Eight of the pairs differed significantly in school motor ability, ten in school process performance and nine in ability to perform ADL. CONCLUSION: This study indicates that there is a difference in overall performance both in ADL and schoolwork task performance between children with complex CHD and healthy children. These findings may suggest that early interventions should be provided for children with complex CHD, who often do not receive such services, in order to enhance participation in childhood ADL and schoolwork.

  • 38.
    Hansson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, T.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Öhlund, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Increased abdominal fat mass and high fat consumption in young school children with congenital heart disease: results from a case-control study2020Ingår i: Journal of human nutrition and dietetics, ISSN 0952-3871, E-ISSN 1365-277X, Vol. 33, nr 4, s. 566-573Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background We have previously found that infants with complex congenital heart disease (CHD) experience growth failure despite high-energy dietary supplementation. This is a follow-up and comparison with healthy controls at 9 years of age regarding body composition and macronutrient intake, especially in relationship to the diet provided during infancy. Methods Anthropometric changes in 10 children with CHD at 12 months and at 4 and 9 years of age were analysed as Z-scores. To assess body composition and food intake at 9 years of age, a dual-energy X-ray absorptiometry scan and a 3-day food diary were completed and compared with age- and gender-matched controls using Wilcoxon's signed-rank test for matched pairs. Results Growth changes from 12 months to 9 years, converted to Z-scores for weight for height and height for age, were significantly different within the group of children with complex CHD, although no growth differences were seen in comparison with healthy controls at 9 years of age. However, the children with CHD had statistically higher abdominal fat mass index and higher daily intake of fat, particularly from saturated fatty acid in g kg-1 compared to controls. Conclusions At 9 years of age, children with complex CHD with growth failure and high fat intake in infancy have normalised growth but increased abdominal fat mass and higher intake of saturated fatty acid compared to their peers. Nutritional monitoring in early childhood may detect unhealthy diet quality and prevent later health risks in this group.

  • 39.
    Hansson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Öhlund, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Fluid restriction negatively affects energy intake and growth in very low birthweight infants with haemodynamically significant patent ductus arteriosus2019Ingår i: Acta Paediatrica, ISSN 0803-5253, E-ISSN 1651-2227, Vol. 108, nr 11, s. 1985-1992Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Aim: We explored if fluid restriction in very low birthweight (VLBW) infants with a haemodynamically significant patent ductus arteriosus (PDA) affected energy and protein intakes and growth.

    Methods: Retrospectively, we identified 90 VLBW infants that were admitted to Umea University Hospital, Sweden, between 2009 and 2012: 42 with and 48 without haemodynamically significant PDA (hsPDA). Anthropometric, fluid, energy and protein intake data during the first 28 days of life were expressed as z‐scores.

    Results: In the 42 infants diagnosed with hsPDA, fluid intake was restricted after diagnosis, resulting in a decrease in energy and protein intake. No decrease was observed in the other 48 infants in the cohort. Multivariate analysis showed that the z‐score of weight change depended on both ductus arteriosus status and energy intake; thus, infants with hsPDA did not grow as expected with the energy provided to them.

    Conclusion: Energy and protein intake was diminished in prematurely born infants with hsPDA when fluid was restricted after diagnosis. The initial reduction in intakes may have contributed to the lower postnatal growth observed in these infants.

  • 40.
    Hansson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stecksen-Blicks, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi, Pedodonti.
    Oral microflora and dietary intake in infants with congenital heart disease: a case control study2012Ingår i: European Archives of Paediatric Dentistry, ISSN 1818-6300, E-ISSN 1996-9805, Vol. 13, nr 5, s. 238-243Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Infants with moderate to severe congenital heart disease (CHD) are at a higher risk for growth failure and malnutrition due to increased metabolic demands and inadequate energy intake. This state requires meals that are more frequent and a special enriched diet, which may have negative implications on oral health.

    AIM: To examine the oral colonisation of some bacteria associated with caries development during infancy; mutans streptococci (MS) and lactobacilli (LCB) in infants with CHD and whether their dietary intake had an impact on the bacterial levels.

    DESIGN: This was a prospective case-control study. 11 infants with CHD and 22 healthy, age-matched infants were enrolled. Saliva samples and food diaries were collected at 6, 9, and 12 months of age. The total viable counts of MS and LCB in saliva were determined, and energy intake, meal frequency, intake of proteins, fat, carbohydrates and sucrose were calculated.

    RESULTS: At 12 months of age, the MS count was higher in the CHD group than in the controls (p<0.01), and MS constituted a higher ratio of the total viable count of oral bacteria (p<0.01). Meal frequency was higher in the CHD group at 6 and 9 months of age than in the controls (p<0.05). The intake of sucrose did not differ between the groups, while the total carbohydrate intake was higher in the control group at 6 and 12 months of age (p<0.05). Compared with the control group, which had six courses of antibiotic administration, the CHD infants had 21 courses (p<0.05).

    CONCLUSIONS: Infants with severe CHD have higher levels of MS at 12 months of age than the healthy controls. A higher meal frequency and use of diuretic medication and antibiotics may have influenced MS colonisation.

  • 41.
    Hansson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sandberg, Camilla
    Umeå universitet, Medicinska fakulteten, Institutionen för samhällsmedicin och rehabilitering, Avdelningen för fysioterapi. Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Avdelningen för medicin.
    Öhlund, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Sthen Bergdahl, Magne
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Rylander Hedlund, Eva
    Department of Women’s and Children’s Health, Division of Pediatric Cardiology, Karolinska Institutet, Stockholm, Sweden.
    Sjöberg, Gunnar
    Department of Women’s and Children’s Health, Division of Pediatric Cardiology, Karolinska Institutet, Stockholm, Sweden.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Vitamin D, liver-related biomarkers, and distribution of fat and lean mass in young patients with Fontan circulation2022Ingår i: Cardiology in the Young, ISSN 1047-9511, E-ISSN 1467-1107, Vol. 32, nr 6, s. 861-868Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Introduction/aim: Young patients with Fontan circulation may have low serum 25-hydroxyvitamin D levels, an affected liver, and unhealthy body compositions. This study aimed to explore the association between vitamin D intake/levels, liver biomarkers, and body composition in young Fontan patients.

    Method: We collected prospective data in 2017 to 2018, obtained with food-frequency questionnaires, biochemical analyses of liver biomarkers, and dual-energy X-ray absorptiometry scans in 44 children with Fontan circulation. Body compositions were compared to matched controls (n = 38). Linear regression analyses were used to investigate associations of biomarkers, leg pain, and lean mass on serum levels of 25-hydroxyvitamin D. Biomarkers were converted to z scores and differences were evaluated within the Fontan patients.

    Results: Our Fontan patients had a daily mean vitamin D intake of 9.9 µg and a mean serum 25-hydroxyvitamin D of 56 nmol/L. These factors were not associated with fat or lean mass, leg pain, or biomarkers of liver status. The Fontan patients had significantly less lean mass, but higher fat mass than controls. Male adolescents with Fontan circulation had a greater mean abdominal fat mass than male controls and higher cholesterol levels than females with Fontan circulation.

    Conclusion: Vitamin D intake and serum levels were not associated with body composition or liver biomarkers in the Fontan group, but the Fontan group had lower lean mass and higher fat mass than controls. The more pronounced abdominal fat mass in male adolescents with Fontan circulation might increase metabolic risks later in life.

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  • 42.
    Hansson, Lena
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Öhlund, Inger
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Lind, Torbjörn
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Stecksén-Blicks, Christina
    Umeå universitet, Medicinska fakulteten, Institutionen för odontologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Dietary intake in infants with complex congenital heart disease: a case-control study on macro- and micronutrient intake, meal frequency and growth2016Ingår i: Journal of human nutrition and dietetics (Print), ISSN 0952-3871, E-ISSN 1365-277X, Vol. 29, nr 1, s. 67-74Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    BACKGROUND: Children with severe congenital heart disease (CHD) need considerable nutritional support to reach normal growth. The actual intake of macro- and micronutrients in outpatient CHD infants over a 6-month period in infancy is not described in the literature. The present study aimed to prospectively investigate the distribution between macro- and micronutrient intake, meal frequency and growth in children with CHD.

    METHODS: At 6, 9 and 12 months of age, a 3-day food diary and anthropometric data were collected in 11 infants with severe CHD and 22 healthy age- and feeding-matched controls. Macro- and micronutrient intake, meal frequency and growth were calculated.

    RESULTS: Compared to the healthy controls, CHD infants had a statistically significantly higher intake of fat at 9 months of age (4.8 versus 3.6 g kg(-1) day(-1) ), a higher percentage energy (E%) from fat, (40.6% versus 34.5%) and a lower E% from carbohydrates (46.1% versus 39.6%) at 12 months of age, and a lower intake of iron (7.22 versus 9.28 mg day(-1) ) at 6 months of age. Meal frequency was significantly higher at 6 and 9 months of age (P < 0.01). Mean Z-score weight for height, weight for age and body mass index for age were significant lower (P < 0.01) at all time points.

    CONCLUSIONS: Despite a higher intake of energy from fat and a higher meal frequency, the intake does not meet the needs for growth, and the results may indicate a low intake of micronutrients in CHD infants.

  • 43. Jansweijer, Joeri A.
    et al.
    van Spaendonck-Zwarts, Karin Y.
    Tanck, Michael W. T.
    van Tintelen, J. Peter
    Christiaans, Imke
    van der Smagt, Jasper
    Vermeer, Alexa
    Bos, J. Martijn
    Moss, Arthur J.
    Swan, Heikki
    Priori, Sylvia
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Tfelt-Hansen, Jacob
    Ackerman, Michael
    Olivotto, Iacopo
    Charron, Philippe
    Gimeno, Juan R.
    van den Berg, Maarten
    Wilde, Arthur
    Pinto, Yigal M.
    Heritability in genetic heart disease: the role of genetic background2019Ingår i: Open heart, E-ISSN 2053-3624, Vol. 6, nr 1, artikel-id e000929Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Mutations in genes encoding ion channels or sarcomeric proteins are an important cause of hereditary cardiac disease. However, the severity of the resultant disease varies considerably even among those with an identical mutation. Such clinical variation is often thought to be explained largely by differences in genetic background or ‘modifier genes’. We aimed to test the prediction that identical genetic backgrounds result in largely similar clinical expression of a cardiac disease causing mutation, by studying the clinical expression of mutations causing cardiac disease in monozygotic twins.

    Methods: We compared first available clinical information on 46 monozygotic twin pairs and 59 control pairs that had either a hereditary cardiomyopathy or channelopathy.

    Results: Despite limited power of this study, we found significant heritability for corrected QT interval (QTc) in long QT syndrome (LQTS). We could not detect significant heritability for structural traits, but found a significant environmental effect on thickness of the interventricular septum in hypertrophic cardiomyopathy.

    Conclusions: Our study confirms previously found robust heritability for electrical traits like QTc in LQTS, and adds information on low or lacking heritability for structural traits in heritable cardiomyopathies. This may steer the search for genetic modifiers in heritable cardiac disease.

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  • 44.
    Jashari, Haki
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lannering, Katarina
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Djekic, Demir
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Mellander, Mats
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Persistent reduced myocardial deformation in neonates after CoA repair2016Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 221, nr 15, s. 886-891Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    INTRODUCTION: Surgical repair of coarctation of the aorta (CoA) is a safe procedure in children, however the condition is known for its potential recurrence and other related complications. The available evidence shows abnormal intrinsic properties of the aorta in CoA, thus suggesting additional effect, even after CoA repair, on left ventricular (LV) function. Accordingly, we sought to obtain a better understanding of LV myocardial mechanics in very early-corrected CoA using two-dimensional STE.

    METHODS AND RESULTS: We retrospectively studied 21 patients with corrected CoA at a median age of 9 (2-53) days at three time points: 1) just before intervention, 2) at short-term follow-up and 3) at medium-term follow-up after intervention and compared them with normal values. Speckle tracking analysis was conducted via vendor independent software, Tomtec. After intervention, LV function significantly improved (from -12.8±3.9 to -16.7±1.7; p<0.001), however normal values were not reached even at medium term follow-up (-18.3±1.7 vs. -20±1.6; p=0.002). Medium term longitudinal strain correlated with pre intervention EF (r=0.58, p=0.006). Moreover, medium term subnormal values were more frequently associated with bicuspid aortic valve (33.3% vs. 66.6%; p<0.05).

    CONCLUSION: LV myocardial function in neonates with CoA can be feasibly evaluated and followed up by speckle tracking echocardiography. LV subendocardial dysfunction however, remains in early infancy coarctation long after repair. Long-term follow-up through adulthood using myocardial deformation measurements should shed light on the natural history and consequences of this anomaly.

  • 45.
    Jashari, Haki
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Lannering, Katarina
    Mellander, Mats
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Henein, Michael Y
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Coarctation repair normalizes left ventricular function and aorto-septal angle in neonates2017Ingår i: Congenital Heart Disease, ISSN 1747-079X, E-ISSN 1747-0803, Vol. 12, nr 2, s. 218-225Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background and aims: Patients with coarctation of the aorta (CoA) have increased left ventricular (LV) afterload that has been shown to impact the LV and ascending aortic function. We aimed to examine the effect of coarctation on LV function and aorto-septal angle (AoSA) before and after surgical repair.

    Methods: We retrospectively studied 21 patients with surgically repaired CoA at a median age of 9 (2-53) days at three time points: (1) just before intervention, (2) at short-term follow-up, and (3) at medium-term follow-up after intervention. AoSA was measured from the parasternal long axisview, at three time points during the cardiac cycle: (1) end diastole, (2) beginning of systole, and (3) at peak ejection in the descending aorta. In addition to conventional LV structure and function, global longitudinal strain, and strain rate were measured using STE technique and Tomtec soft-ware. Three groups of age matched healthy children served as controls at each time point.

    Results: AoSA was significantly wider before intervention, in particular at peak ejection in the descending aorta (1448 6 6.48 vs. 1368 6 4.18; P < .0001), and correlated with CoA pressure gradi-ent. After intervention, AoSA normalized and significantly correlated with the increase of LV cavity function and overall LV deformation parameters.

    Conclusions: AoSA is abnormally wide in neonates with CoA and is associated with severity ofobstruction, LV dysfunction and compromised LV global deformation.

  • 46.
    Jashari, Haki
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bajraktari, Gani
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Left ventricular response to pressure afterload in children: aortic stenosis and coarctation A systematic review of the current evidence2015Ingår i: International Journal of Cardiology, ISSN 0167-5273, E-ISSN 1874-1754, Vol. 178, s. 203-209Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Congenital aortic stenosis (CAS) and Coarctation of Aorta (CoA) represent two forms of pressure afterload that affect the left ventricle (LV), hence require regular echocardiographic monitoring. Subclinical dysfunction of the LV exists even in asymptomatic patients with preserved left ventricular ejection fraction (EF), implying low sensitivity of EF in predicting optimum time for intervention. In this article we review patterns of LV myocardial deformation before and after correction of CAS and CoA in infants, children and adolescents, showing their important role in monitoring the course of LV dysfunction. A systematic search using PubMed was performed and suitable studies are presented on a narrative form. Normal EF and/or fractional shortening (FS), with subclinical myocardial dysfunction are reported in all studies before intervention. The short-term results, after intervention, were related to the type of procedure, with no improvement or further deterioration related to surgery but immediate improvement after balloon intervention. Long term follow-up showed further improvement but still subnormal function. Thus correction of CAS and CoA before irreversible LV dysfunction is vital, and requires longitudinal studies in order to identify the most accurate parameter for function prognostication. Until then, conventional echocardiographic parameters together with myocardial velocities and deformation parameters should continue to provide follow-up reproducible measures of ventricular function.

  • 47.
    Jashari, Haki
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Ibrahimi, Pranvera
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Bajraktari, Gani
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Kryeziu, Lindita
    Jashari, Fisnik
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Henein, Michael Y.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Normal ranges of left ventricular strain in children: a meta-analysis2015Ingår i: Cardiovascular Ultrasound, E-ISSN 1476-7120, Vol. 13, artikel-id 37Artikel, forskningsöversikt (Refereegranskat)
    Abstract [en]

    Aims: The definition of normal values of two-dimensional speckle-tracking echocardiography derived left ventricular (LV) deformation parameters, is of critical importance for the routine application of this modality in children. The objectives of this study were to perform a meta-analysis of normal ranges for longitudinal, circumferential and radial strain/strain rate values and to identify confounders that may contribute to differences in reported measures. Methods and Results: A systematic search was conducted. Studies describing normal healthy subjects and observational studies that used control groups as a comparison were included. Data were combined using a random-effect model. Effects of demographic, clinical and equipment variables were assessed through meta-regression. The search identified 1,192 subjects form 28 articles. Longitudinal strain (LS) normal mean values varied from -12.9 to -26.5 (mean, -20.5; 95 % CI, -20.0 to -21.0). Normal mean values of circumferential strain (CS) varied from -10.5 to -27.0 (mean, -22.06; 95 % CI, -21.5 to -22.5). Radial strain (RS) normal mean values varied from 24.9 to 62.1 (mean, 45.4; 95 % CI, 43.0 to 47.8). Meta-regression showed LV end diastolic diameter as a significant determinant of variation for LS. Longitudinal systolic strain rate (LSRs) was significantly determined by the age and RS by the type of vendor used. Conclusion: Variations among different normal ranges were dependent on the vendor used, LV end-diastolic diameter and age. Vendor-independent software for analyzing myocardial deformation in children, using images from different vendors would be the ideal solution for strain measurements or else using the same system for patient's follow up.

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  • 48.
    Kaizer, Alexander M.
    et al.
    Biostatistics and Informatics, Colorado School of Public Health, University of Colorado-Anschutz Medical Campus, CO, Aurora, United States.
    Winbo, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Department of Physiology, University of Auckland, Auckland, New Zealand.
    Clur, Sally-Ann B
    Department of Pediatric Cardiology, Emma Children's Hospital, Amsterdam University Medical Centers, Amsterdam, Netherlands; Department of Cardiology, University Medical Center, Amsterdam, Netherlands.
    Etheridge, Susan P.
    Department of Pediatrics, Division of Cardiology, University of Utah School of Medicine, UT, Salt Lake City, United States.
    Ackerman, Michael J.
    Department of Cardiovascular Medicine, Division of Heart Rhythm Services, Mayo Clinic, MN, Rochester, United States; Department of Pediatric and Adolescent Medicine, Division of Pediatric Cardiology, Mayo Clinic, MN, Rochester, United States; Department of Molecular Pharmacology & Experimental Therapeutics, Mayo Clinic, MN, Rochester, United States; Mayo Clinic, Windland Smith Rice Genetic Heart Rhythm Clinic and Windland Smith Rice Sudden Death Genomics Laboratory, MN, Rochester, United States.
    Horigome, Hitoshi
    Department of Pediatrics, Section of Cardiology, Tsukuba University, Tsukuba, Japan.
    Herberg, Ulrike
    Department of Pediatric Cardiology, RWTH University Hospital Aachen, Aachen, Germany; Department of Pediatric Cardiology, University Hospital Bonn, Bonn, Germany.
    Dagradi, Federica
    Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Via Pier Lombardo 22, Milan, Italy.
    Spazzolini, Carla
    Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Via Pier Lombardo 22, Milan, Italy.
    Killen, Stacy A S
    Department of Pediatrics, Division of Cardiology, Vanderbilt University Medical Center, TN, Nashville, United States.
    Wacker-Gussmann, Annette
    Department of Congenital Heart Disease and Paediatric Cardiology, German Heart Center, Munich, Germany.
    Wilde, Arthur A M
    Department of Cardiology, University Medical Center, Amsterdam, Netherlands; Department of Cardiology, Amsterdam UMC Location University of Amsterdam, Amsterdam, Netherlands; Department of Cardiology, Amseterdam University Medical Center, Amsterdam, Netherlands.
    Sinkovskaya, Elena
    Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School, VA, Norfolk, United States.
    Abuhamad, Alfred
    Department of Obstetrics and Gynecology, Division of Maternal-Fetal Medicine, Eastern Virginia Medical School, VA, Norfolk, United States.
    Torchio, Margherita
    Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Via Pier Lombardo 22, Milan, Italy.
    Ng, Chai-Ann
    Mark Cowley Lidwill Research Program in Cardiac Electrophysiology, Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia; School of Clinical Medicine, UNSW Sydney, Darlinghurst, NSW, Australia.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik. Department of Cardiology, University Medical Center, Amsterdam, Netherlands.
    Schwartz, Peter J.
    Center for Cardiac Arrhythmias of Genetic Origin and Laboratory of Cardiovascular Genetics, IRCCS Istituto Auxologico Italiano, Via Pier Lombardo 22, Milan, Italy.
    Cuneo, Bettina F.
    Department of Pediatrics, Section of Cardiology, University of Denver School of Medicine, 13123 16th Ave, Box 100, Aurora, CO 80045, USA.
    Effects of cohort, genotype, variant, and maternal β-blocker treatment on foetal heart rate predictors of inherited long QT syndrome2023Ingår i: Europace, ISSN 1099-5129, E-ISSN 1532-2092, Vol. 25, nr 11, artikel-id euad319Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    AIMS: In long QT syndrome (LQTS), primary prevention improves outcome; thus, early identification is key. The most common LQTS phenotype is a foetal heart rate (FHR) < 3rd percentile for gestational age (GA) but the effects of cohort, genotype, variant, and maternal β-blocker therapy on FHR are unknown. We assessed the influence of these factors on FHR in pregnancies with familial LQTS and developed a FHR/GA threshold for LQTS.

    METHODS AND RESULTS: In an international cohort of pregnancies in which one parent had LQTS, LQTS genotype, familial variant, and maternal β-blocker effects on FHR were assessed. We developed a testing algorithm for LQTS using FHR and GA as continuous predictors. Data included 1966 FHRs at 7-42 weeks' GA from 267 pregnancies/164 LQTS families [220 LQTS type 1 (LQT1), 35 LQTS type 2 (LQT2), and 12 LQTS type 3 (LQT3)]. The FHRs were significantly lower in LQT1 and LQT2 but not LQT3 or LQTS negative. The LQT1 variants with non-nonsense and severe function loss (current density or β-adrenergic response) had lower FHR. Maternal β-blockers potentiated bradycardia in LQT1 and LQT2 but did not affect FHR in LQTS negative. A FHR/GA threshold predicted LQT1 and LQT2 with 74.9% accuracy, 71% sensitivity, and 81% specificity.

    CONCLUSION: Genotype, LQT1 variant, and maternal β-blocker therapy affect FHR. A predictive threshold of FHR/GA significantly improves the accuracy, sensitivity, and specificity for LQT1 and LQT2, above the infant's a priori 50% probability. We speculate this model may be useful in screening for LQTS in perinatal subjects without a known LQTS family history.

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  • 49.
    Karlsson, Marcus
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Hörnsten, Rolf
    Umeå universitet, Medicinska fakulteten, Institutionen för kirurgisk och perioperativ vetenskap, Klinisk fysiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Wiklund, Urban
    Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Radiofysik.
    Automatic filtering of outliers in RR intervals before analysis of heart rate variability in Holter recordings: a comparison with carefully edited data.2012Ingår i: Biomedical engineering online, E-ISSN 1475-925X, Vol. 11, nr 2, s. 12-Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Background: Undetected arrhythmic beats seriously affect the power spectrum of the heart rate variability (HRV). Therefore, the series of RR intervals are normally carefully edited before HRV is analysed, but this is a time consuming procedure when 24-hours recordings are analysed. Alternatively, different methods can be used for automatic removal of arrhythmic beats and artefacts. This study compared common frequency domain indices of HRV when determined from manually edited and automatically filtered RR intervals.

    Methods and Results: Twenty-four hours Holter recordings were available from 140 healthy subjects of age 1-75 years. An experienced technician carefully edited all recordings. Automatic filtering was performed using a recursive procedure where RR intervals were removed if they differed from the mean of the surrounding RR intervals with more than a predetermined limit (ranging from 10% to 50%). The filtering algorithm was evaluated by replacing 1% of the beats with synthesised ectopic beats. Power spectral analysis was performed before and after filtering of both the original edited data and the noisy data set. The results from the analysis using the noisy data were used to define an age-based filtering threshold. The age-based filtration was evaluated with completely unedited data, generated by removing all annotations from the series of RR intervals, and then comparing the resulting HRV indices with those obtained using edited data. The results showed equivalent results after age-based filtration of both the edited and unedited data sets, where the differences in HRV indices obtained by different preprocessing methods were small compared to the mean values within each age group.

    Conclusions: The study showed that it might not be necessary to perform the time-consuming careful editing of all detected heartbeats before HRV is analysed in Holter recordings.

    In most subjects, it is sufficient to perform the regular editing needed for valid arrhythmia analyses, and then remove undetected ectopic beats and artefacts by age-based filtration of the series of RR intervals, particularly in subjects older than 30 years.

  • 50.
    Kesek, Milos
    et al.
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Rydberg, Annika
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Pediatrik.
    Jensen, Steen M
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Kardiologi.
    Two Cases of LQT Syndrome with Malignant Syncope after Switch from Propranolol to Bisoprolol2016Ingår i: Pacing and Clinical Electrophysiology, ISSN 0147-8389, E-ISSN 1540-8159, Vol. 39, nr 3, s. 305-306Artikel i tidskrift (Refereegranskat)
    Abstract [en]

    Propranolol in slow-release form has been the first-line treatment in long QT (LQT) until it was withdrawn from the market. We describe two cases where a switch to bisoprolol resulted in worsening of arrhythmia control: A man with LQT2, asymptomatic on propranolol, experienced syncope after switching to bisoprolol 5 mg daily. He switched back to propranolol and has remained asymptomatic during subsequent 12 months. A man with classical Jervell Lange-Nielsen syndrome, previous gangliectomy, and ICD implantation, switched to bisoprolol 5 mg daily. Four months later he experienced a tachycardia storm. He switched back to propranolol and has remained free from arrhythmias during subsequent 12 months.

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