Publications by authors named "Annika Rydberg"

66 Publications

Calf Muscle Oxygenation is Impaired and May Decline with Age in Young Patients with Total Cavopulmonary Connection.

Pediatr Cardiol 2021 Oct 8. Epub 2021 Oct 8.

Department of Public Health and Clinical Medicine, Medicine, Umeå University, Umeå, Sweden.

Patients palliated with Total Cavopulmonary Connection have a lower muscle mass and a lower exercise capacity. We assessed calf muscle oxidative metabolism during and after heel raise exercise to exhaustion in young patients with TCPC compared to healthy peers. Near-infrared spectroscopy was used for measuring oxygen metabolism in the medial portion of the gastrocnemius muscle. Forty-three patients with TCPC, aged 6-18 years, were compared with 43 age and sex-matched healthy control subjects. Subgroups were formed to include children (6-12 years) and adolescents (13-18 years) to determine if these age groups influenced the results. During exercise, for the patients compared to controls there was a lower increase in deoxygenated hemoglobin (oxygen extraction) (5.13 ± 2.99au vs. 7.75 ± 4.15au, p = 0.001) and a slower rate of change in total hemoglobin (blood volume) (0.004 ± 0.015au vs 0.016 ± 0.01au, p = 0.001). Following exercise, patients exhibited a slower initial increase in tissue oxygenation saturation index (0.144 ± 0.11au vs 0.249 ± 0.226au, p = 0.007) and a longer half-time to maximum hyperemia (23.7 ± 11.4 s vs 16.8 ± 7.5 s, p = 0.001). On the subgroup level, the adolescents differed compared to healthy peers, whereas the children did not. Young patients with TCPC had impaired oxidative metabolism during exercise and required a longer time to recover. In that the differences were seen in the adolescent group and not in the children group may indicate a declining function with age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-021-02743-6DOI Listing
October 2021

Vitamin D, liver-related biomarkers, and distribution of fat and lean mass in young patients with Fontan circulation.

Cardiol Young 2021 Aug 2:1-8. Epub 2021 Aug 2.

Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951121003115DOI Listing
August 2021

Functional hyperactivity in long QT syndrome type 1 pluripotent stem cell-derived sympathetic neurons.

Am J Physiol Heart Circ Physiol 2021 07 18;321(1):H217-H227. Epub 2021 Jun 18.

Department of Physiology, University of Auckland, Auckland, New Zealand.

Sympathetic activation is an established trigger of life-threatening cardiac events in long QT syndrome type 1 (LQT1). loss-of-function variants, which underlie LQT1, have been associated with both cardiac arrhythmia and neuronal hyperactivity pathologies. However, the LQT1 sympathetic neuronal phenotype is unknown. Here, we aimed to study human induced pluripotent stem cell (hiPSC)-derived sympathetic neurons (SNs) to evaluate neuronal functional phenotype in LQT1. We generated hiPSC-SNs from two patients with LQT1 with a history of sympathetically triggered arrhythmia and loss-of-function genotypes (c.781_782delinsTC and p.S349W/p.R518X). Characterization of hiPSC-SNs was performed using immunohistochemistry, enzyme-linked immunosorbent assay, and whole cell patch clamp electrophysiology, and functional LQT1 hiPSC-SN phenotypes compared with healthy control (WT) hiPSC-SNs. hiPSC-SNs stained positive for tyrosine hydroxylase, peripherin, KCNQ1, and secreted norepinephrine. hiPSC-SNs at 60 ± 2.2 days in vitro had healthy resting membrane potentials (-60 ± 1.3 mV), and fired rapid action potentials with mature kinetics in response to stimulation. Significant hyperactivity in LQT1 hiPSC-SNs was evident via increased norepinephrine release, increased spontaneous action potential frequency, increased total inward current density, and reduced afterhyperpolarization, compared with age-matched WT hiPSC-SNs. A significantly higher action potential frequency upon current injection and larger synaptic current amplitudes in compound heterozygous p.S349W/p.R518X hiPSC-SNs compared with heterozygous c.781_782delinsTC hiPSC-SNs was also observed, suggesting a potential genotype-phenotype correlation. Together, our data reveal increased neurotransmission and excitability in heterozygous and compound heterozygous patient-derived LQT1 sympathetic neurons, suggesting that the cellular arrhythmogenic potential in LQT1 is not restricted to cardiomyocytes. Here, we present the first study of patient-derived LQT1 sympathetic neurons that are norepinephrine secreting, and electrophysiologically functional, in vitro. Our data reveal a novel LQT1 sympathetic neuronal phenotype of increased neurotransmission and excitability. The identified sympathetic neuronal hyperactivity phenotype is of particular relevance as it could contribute to the mechanisms underlying sympathetically triggered arrhythmia in LQT1.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1152/ajpheart.01002.2020DOI Listing
July 2021

Changes in Heart Rate and Heart Rate Variability During Surgical Stages to Completed Fontan Circulation.

Pediatr Cardiol 2021 Jun 10;42(5):1162-1169. Epub 2021 Apr 10.

Department of Clinical Sciences, Pediatrics, Umeå University, 90185, Umeå, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-021-02595-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192394PMC
June 2021

Right Heart Structure, Geometry and Function Assessed by Echocardiography in 6-Year-Old Children Born Extremely Preterm-A Population-Based Cohort Study.

J Clin Med 2020 Dec 31;10(1). Epub 2020 Dec 31.

Department of Pediatric Cardiology, Sachs' Children and Youth Hospital, Södersjukhuset, 118 83 Stockholm, Sweden.

Preterm birth has been associated with altered cardiac phenotype in adults. Our aim was to test the hypothesis that children surviving extremely preterm birth have important structural or functional changes of the right heart or pulmonary circulation. We also examined relations between birth size, gestational age, neonatal diagnoses of bronchopulmonary dysplasia (BPD) and patent ductus arteriosus (PDA) with cardiac outcomes. We assessed a population-based cohort of children born in Sweden before 27 weeks of gestation with echocardiography at 6.5 years of age ( = 176). Each preterm child was matched to a healthy control child born at term. Children born preterm had significantly smaller right atria, right ventricles with smaller widths, higher relative wall thickness and higher estimated pulmonary vascular resistance (PVR) than controls. In preterm children, PVR and right ventricular myocardial performance index (RVmpi') were significantly higher in those with a PDA as neonates than in those without PDA, but no such associations were found with BPD. In conclusion, children born extremely preterm exhibit higher estimated PVR, altered right heart structure and function compared with children born at term.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10010122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795537PMC
December 2020

Exercise Induced Worsening of Mechanical Heterogeneity and Diastolic Impairment in Long QT Syndrome.

J Clin Med 2020 Dec 24;10(1). Epub 2020 Dec 24.

Institute of Public Health and Clinical Medicine, Umea University, 90187 Umea, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm10010037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7795719PMC
December 2020

QT correction using Bazett's formula remains preferable in long QT syndrome type 1 and 2.

Ann Noninvasive Electrocardiol 2021 01 18;26(1):e12804. Epub 2020 Oct 18.

Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/anec.12804DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816807PMC
January 2021

Enhancing rare variant interpretation in inherited arrhythmias through quantitative analysis of consortium disease cohorts and population controls.

Genet Med 2021 01 7;23(1):47-58. Epub 2020 Sep 7.

Member of the European Reference Network for rare, low prevalence and/or complex diseases of the heart: ERN GUARD-Heart, Amsterdam, Netherlands.

Purpose: Stringent variant interpretation guidelines can lead to high rates of variants of uncertain significance (VUS) for genetically heterogeneous disease like long QT syndrome (LQTS) and Brugada syndrome (BrS). Quantitative and disease-specific customization of American College of Medical Genetics and Genomics/Association for Molecular Pathology (ACMG/AMP) guidelines can address this false negative rate.

Methods: We compared rare variant frequencies from 1847 LQTS (KCNQ1/KCNH2/SCN5A) and 3335 BrS (SCN5A) cases from the International LQTS/BrS Genetics Consortia to population-specific gnomAD data and developed disease-specific criteria for ACMG/AMP evidence classes-rarity (PM2/BS1 rules) and case enrichment of individual (PS4) and domain-specific (PM1) variants.

Results: Rare SCN5A variant prevalence differed between European (20.8%) and Japanese (8.9%) BrS patients (p = 5.7 × 10) and diagnosis with spontaneous (28.7%) versus induced (15.8%) Brugada type 1 electrocardiogram (ECG) (p = 1.3 × 10). Ion channel transmembrane regions and specific N-terminus (KCNH2) and C-terminus (KCNQ1/KCNH2) domains were characterized by high enrichment of case variants and >95% probability of pathogenicity. Applying the customized rules, 17.4% of European BrS and 74.8% of European LQTS cases had (likely) pathogenic variants, compared with estimated diagnostic yields (case excess over gnomAD) of 19.2%/82.1%, reducing VUS prevalence to close to background rare variant frequency.

Conclusion: Large case-control data sets enable quantitative implementation of ACMG/AMP guidelines and increased sensitivity for inherited arrhythmia genetic testing.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41436-020-00946-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790744PMC
January 2021

Left Ventricular Contraction Duration Is the Most Powerful Predictor of Cardiac Events in LQTS: A Systematic Review and Meta-Analysis.

J Clin Med 2020 Aug 31;9(9). Epub 2020 Aug 31.

Institute of Public Health and Clinical Medicine, Umeå University, 90187 Umeå, Sweden.

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 (QT, QT 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-QT, WMD 72.8; QT 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 QT 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/jcm9092820DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7565502PMC
August 2020

Impaired knee extension muscle strength in adolescents but not in children with Fontan circulation.

Cardiol Young 2020 Aug 23;30(8):1138-1143. Epub 2020 Jun 23.

Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden.

Introduction: Impaired isometric muscle strength was previously reported in adults with Fontan circulation. However, it is unclear if this impairment is present in children and adolescents with Fontan circulation. We investigated isometric muscle strength of the lower limb in patients (6-18 years) with Fontan circulation in comparison with healthy controls.

Method: In this cross-sectional study, 43 patients (6-18 years) with Fontan circulation and 43 age- and sex-matched controls were included. Isometric knee extension and plantar flexion muscle strength were assessed using dynamometry (Newton, N). Lean mass of the legs was assessed with dual-energy X-ray absorptiometry. Analyses were performed on group level (n = 43), and for subgroups that included children aged 6-12 years (n = 18) and adolescents aged 13-18 years (n = 25).

Results: On group level, the patients with Fontan circulation had impaired isometric knee extension strength in comparison with the controls (p = 0.03). In subgroup analyses, impaired isometric knee extension strength was present in the adolescents (p = 0.009) but not in the children groups. For plantar flexion, there was no difference between patients and controls. There was no difference in lean mass between patients and controls (9.6 ± 4.3 kg vs. 10.8 ± 5.6 kg, p = 0.31). However, the lean mass was highly correlated to isometric knee extension strength (patients r = 0.89, controls r = 0.96, p < 0.001) and isometric plantar flexion strength (patients r = 0.7, controls r = 0.81, p < 0.001).

Conclusion: The finding of impaired isometric knee extension muscle strength in adolescents (13-18 years) with Fontan circulation and no corresponding impairment in the children group (6-12 years) could imply that isometric muscle strength gets more impaired with age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951120001675DOI Listing
August 2020

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

Circulation 2020 07 20;142(4):324-338. Epub 2020 May 20.

Masonic Medical Research Institute, Utica, NY (R.P.).

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility.

Methods: We conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score.

Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (<5×10) near , , and , and 1 missense variant in (p.Asp85Asn) at the suggestive threshold (<10). Heritability analyses showed that ≈15% of variance in overall LQTS susceptibility was attributable to common genetic variation ( 0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r=0.40; =3.2×10). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (<0.005).

Conclusions: This work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCULATIONAHA.120.045956DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7382531PMC
July 2020

Outpatient volumes and medical staffing resources as predictors for continuity of follow-up care during transfer of adolescents with congenital heart disease.

Int J Cardiol 2020 07 17;310:51-57. Epub 2020 Jan 17.

Institute of Health and Care Sciences, University of Gothenburg, Arvid Wallgrens Backe, Box 457, 405 30 Gothenburg, Sweden; Department of Paediatric Cardiology, Queen Silvia's Children's Hospital, Rondvägen 10, 416 50 Gothenburg, Sweden. Electronic address:

Background: Providing continuous follow-up care to patients with congenital heart disease (CHD) remains a challenge in many settings. Previous studies highlight that patients with CHD experience discontinuation of follow-up care, but mainly describe a single-centre perspective, neglecting inter-institutional variations. Hospital-related factors above and beyond patient-related factors are believed to affect continuity of care. The present multicentre study therefore investigated (i) proportion of "no follow-up care"; (ii) transfer destinations after leaving paediatric cardiology; (iii) variation in proportions of no follow-up between centres; (iv) the association between no follow-up and outpatient volumes, and (v) its relationship with staffing resources at outpatient clinics.

Methods: An observational, multicentre study was conducted in seven university hospitals. In total, 654 adolescents with CHD, born between 1991 and 1993, with paediatric outpatient visit at age 14-18 years were included. Transfer status was determined 5 years after the intended transfer to adult care (23y), based on medical files, self-reports and registries.

Results: Overall, 89.7% of patients were receiving adult follow-up care after transfer; 6.6% had no follow-up; and 3.7% were untraceable. Among patients in follow-up care, only one remained in paediatric care and the majority received specialist adult CHD care. Significant variability in proportions of no follow-up were identified across centres. Higher outpatient volumes at paediatric outpatient clinics were associated with better continued follow-up care after transfer (OR = 1.061; 95% CI = 1.001 - 1.124). Medical staffing resources were not found predictive.

Conclusion: Our findings support the theory of hospital-related factors influencing continuity of care, above and beyond patient-related characteristics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijcard.2020.01.016DOI Listing
July 2020

Transplantation-free survival after Norwood surgery for hypoplastic left heart syndrome with aortic atresia: A Swedish national cohort study.

Cardiol Young 2020 Mar 10;30(3):353-360. Epub 2020 Jan 10.

Department of Paediatric Cardiology, Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.

Background: Norwood surgery has been available in Sweden since 1993. In this national cohort study, we analysed transplantation-free survival after Norwood surgery for hypoplastic left heart syndrome with aortic atresia.

Methods: Patients were identified from the complete national cohort of live-born with hypoplastic left heart syndrome/aortic atresia 1993-2010. Analysis of survival after surgery was performed using Cox proportional hazards models for the total cohort and for birth period and gender separately. Thirty-day mortality and inter-stage mortality were analysed. Patients were followed until September 2016.

Results: The 1993-2010 cohort consisted of 208 live-born infants. Norwood surgery was performed in 121/208 (58%). The overall transplantation-free survival was 61/121 (50%). The survival was higher in the late period (10-year survival 63%) than in the early period (10-year survival 40%) (p = 0.010) and lower for female (10-year survival 34%) than for male patients (10-year survival 59%) (p = 0.002). Inter-stage mortality between stages I and II decreased from 23 to 8% (p = 0.008). For male patients, low birthweight in relation to gestational age was a factor associated with poor outcome.

Conclusion: The survival after Norwood surgery for hypoplastic left heart syndrome/aortic atresia improved by era of surgery, mainly explained by improved survival between stages I and II. Female gender was a significant risk factor for death or transplantation. For male patients, there was an increased risk of death when birthweight was lower than expected in relation to gestational age.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951119003263DOI Listing
March 2020

Lung function and pulmonary vascular resistance are not associated in 6-year-old children born extremely preterm.

Acta Paediatr 2020 04 10;109(4):746-753. Epub 2019 Oct 10.

Division of Paediatrics, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.

Aim: Children born preterm are at increased risk of reduced lung function. The aim was to test whether lung function was associated with pulmonary vascular resistance.

Methods: Participants were recruited from a population-based cohort born in 2004-2007. Lung function was assessed with spirometry after administration of a beta2-agonist. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV ) were determined. Estimations of pulmonary vascular resistance, arterial dimensions, right ventricular wall thickness, sphericity, and systolic (TAPSE) and diastolic functions were performed with echocardiography. Adjusted regression analyses were used to study associations.

Results: Sixty-six children (33 boys) born at 22-26 weeks of gestational age (birthweights 460-1134 g) were assessed at a mean age of 6.7 years. Despite large variations in lung function with FVC z-scores ranging from -4.6 to +2.8, there were no associations between lung function and pulmonary arterial pressure, right ventricular structure or function. Children with higher FVC z-scores (r = .52, β = .55 mm, P = .015) and higher FEV z-scores (r = .58, β = .73 mm, P = .001) exhibited larger pulmonary arteries.

Conclusion: In children born extremely preterm, lung function was not associated with pulmonary vascular resistance. Routine echocardiographic evaluation of extremely preterm children may not be indicated at age 6.5 years.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apa.15030DOI Listing
April 2020

Mothers with long QT syndrome are at increased risk for fetal death: findings from a multicenter international study.

Am J Obstet Gynecol 2020 03 11;222(3):263.e1-263.e11. Epub 2019 Sep 11.

IRCCS Istituto Auxologico Italiano, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy.

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 databases 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ajog.2019.09.004DOI Listing
March 2020

Ready for Transfer to Adult Care? A Triadic Evaluation of Transition Readiness in Adolescents With Congenital Heart Disease and Their Parents.

J Fam Nurs 2019 08 25;25(3):447-468. Epub 2019 Jul 25.

3 University of Gothenburg, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1074840719864255DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6724455PMC
August 2019

Exercise worsening of electromechanical disturbances: A predictor of arrhythmia in long QT syndrome.

Clin Cardiol 2019 Jul 18;42(7):701. Epub 2019 Jun 18.

Institute of Public Health and Clinical Medicine, Umea University, Sweden.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23216DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6605001PMC
July 2019

Heritability in genetic heart disease: the role of genetic background.

Open Heart 2019;6(1):e000929. Epub 2019 May 28.

Heart Center, Clinical and Experimental Cardiology, Amsterdam UMC, University of Amsterdam, Amsterdam, Netherlands.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1136/openhrt-2018-000929DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6546190PMC
February 2021

Adverse events within 1 year after surgical and percutaneous closure of atrial septal defects in preterm children.

Cardiol Young 2019 May 4;29(5):626-636. Epub 2019 Jun 4.

Department of Clinical Sciences, Unit of Paediatrics,Umeå University,Umeå,Sweden.

Introduction: Atrial septal defect is the third most common CHD. A hemodynamically significant atrial septal defect causes volume overload of the right side of the heart. Preterm children may suffer from both pulmonary and cardiac comorbidities, including altered myocardial function. The aim of this study was to compare the rate of adverse events following atrial septal defect closure in preterm- and term-born children.

Method: We performed a retrospective cohort study including children born in Sweden, who had a surgical or percutaneous atrial septal defect closure at the children's hospitals in Lund and Stockholm, between 2000 and 2014, assessing time to the first event within 1 month or 1 year. We analysed differences in the number of and the time to events between the preterm and term cohort using the Kaplan-Meier survival curve, a generalised model applying zero-inflated Poisson distribution and Gary-Anderson's method.

Results: Overall, 413 children were included in the study. Of these, 93 (22.5%) were born prematurely. The total number of adverse events was 178 (110 minor and 68 major). There was no difference between the cohorts in the number of events, whether within 1 month or within a year, between major (p = 0.69) and minor (p = 0.84) events or frequencies of multiple events (p = 0.92).

Conclusion: Despite earlier procedural age, larger atrial septal defects, and higher comorbidity than term children, preterm children appear to have comparable risk for complications during the first year after surgical or percutaneous closure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1017/S1047951119000350DOI Listing
May 2019

Fluid restriction negatively affects energy intake and growth in very low birthweight infants with haemodynamically significant patent ductus arteriosus.

Acta Paediatr 2019 11 23;108(11):1985-1992. Epub 2019 May 23.

Department of Clinical Science, Paediatrics, Umeå University, Umeå, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/apa.14815DOI Listing
November 2019

Sinus node dysfunction in patients with Fontan circulation: could heart rate variability be a predictor for pacemaker implantation?

Pediatr Cardiol 2019 Apr 27;40(4):685-693. Epub 2019 Mar 27.

Department of Clinical Sciences, Pediatrics, Umeå University, 901 85, Umeå, Sweden.

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 Poincaré 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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00246-019-02092-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451711PMC
April 2019

Pacemaker treatment after Fontan surgery-A Swedish national study.

Congenit Heart Dis 2019 Jul 18;14(4):582-589. Epub 2019 Mar 18.

Department of Clinical Sciences, Umeå University, Umeå, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/chd.12766DOI Listing
July 2019

Patient empowerment and its correlates in young persons with congenital heart disease.

Eur J Cardiovasc Nurs 2019 06 5;18(5):389-398. Epub 2019 Mar 5.

1 Institute of Health and Care Sciences, University of Gothenburg, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/1474515119835434DOI Listing
June 2019

Changing Epidemiology of Hypoplastic Left Heart Syndrome: Results of a National Swedish Cohort Study.

J Am Heart Assoc 2019 01;8(2):e010893

1 Department of Paediatric Cardiology Queen Silvia Children's Hospital Sahlgrenska University Hospital Gothenburg Sweden.

Background Norwood surgery provides a palliative surgical option for hypoplastic left heart syndrome and has been available in Sweden since 1993. The practice of prenatal ultrasound screening was gradually implemented in the same era, resulting in an increased prenatal detection rate. Our primary aims were to study changes in the incidence of live births, prenatal detection rate, and the termination of pregnancies over time. The secondary aims were to study the proportion of live-borns undergoing surgery and to identify factors that influenced whether surgery was or was not performed. Methods and Results Neonates with hypoplastic left heart syndrome with aortic atresia born 1990-2010 were identified through national databases, surgical files, and medical records. The fetal incidence was estimated from the period when prenatal screening was rudimentary. The study period was divided into the presurgical, early surgical, and late surgical periods. The incidence was calculated as the overall yearly incidence for each time period and sex separately. Factors influencing whether surgery was performed were analyzed using Cox-logistic regression. The incidence at live birth decreased from 15.4 to 8.4 per 100 000. The prenatal detection rate increased from 27% to 63%, and terminations increased from 19% to 56%. The odds of having surgery was higher in the late period and higher in the group with prenatal diagnosis. Conclusions We observed a decrease in incidence of live-borns with hypoplastic left heart syndrome aortic atresia. There was in increase in prenatal detection rate and an increase in termination of pregnancy. The proportion of live-borns who underwent surgery increased between time periods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/JAHA.118.010893DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497328PMC
January 2019

Exercise worsening of electromechanical disturbances: A predictor of arrhythmia in long QT syndrome.

Clin Cardiol 2019 Feb 22;42(2):235-240. Epub 2018 Dec 22.

Institute of Public Health and Clinical Medicine, Umea University, Umea, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/clc.23132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6712344PMC
February 2019

Parental uncertainty about transferring their adolescent with congenital heart disease to adult care.

J Adv Nurs 2019 Feb 18;75(2):380-387. Epub 2018 Oct 18.

Institute of Health and Care Sciences, University of Gothenburg, Gothenburg, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/jan.13852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7379976PMC
February 2019

Fetal heart rate reflects mutation burden and clinical outcome in twin probands with mutations.

HeartRhythm Case Rep 2018 Jun 5;4(6):237-240. Epub 2018 Apr 5.

Department of Clinical Sciences, Division of Pediatrics, Umeå University, Umeå, Sweden.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.hrcr.2018.02.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6006493PMC
June 2018

Left Ventricular Isovolumetric Relaxation Time Is Prolonged in Fetal Long-QT Syndrome.

Circ Arrhythm Electrophysiol 2018 04;11(4):e005797

Departments of Pediatric Cardiology, Obstetrics and Gynecology, and Cardiology, Academic Medical Center, Amsterdam, The Netherlands (S.-A.B.C., A.S.V., P.G.R.d.M., A.A.W., N.A.B.). Department of Pediatric Cardiology, University of Utah & Primary Children's Hospital, Salt Lake City (S.P.E.). Department of Clinical Sciences, Pediatrics, Umeå University, Sweden (A.R.). Department of Cardiology, Mayo Clinic, Rochester, MN (M.J.A.). Department of Pediatrics, Medical College of Wisconsin, Milwaukee (D.W.B.). Department of Pediatric Cardiology, University of Bonn, Germany (U.H.). Pediatric Cardiology, Children's National Medical Center, Washington, DC (M.T.D.). The Heart Institute, Department of Pediatrics, Children's Hospital Colorado, Denver (B.F.C.).

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: LV isovolumetric contraction time, LV ejection time, LVIRT, cycle length, and FHR were measured using pulsed Doppler waveforms in fetuses. Time intervals were expressed as percentages of cycle length, and the LV myocardial performance index was calculated. Single measurements were stratified by gestational age and compared between LQTS fetuses and controls. Receiver-operator curves were performed for FHR and normalized LVIRT (N-LVIRT). A linear mixed-effect model including multiple measurements was used to analyze trends in FHR, N-LVIRT, and LV myocardial performance index. There were 33 LQTS fetuses and 469 controls included. In LQTS fetuses, the LVIRT was prolonged in all gestational age groups (<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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1161/CIRCEP.117.005797DOI Listing
April 2018

Abnormal ventricular repolarization in long QT syndrome carriers is related to short left ventricular filling time and attenuated stroke volume response during exercise.

Echocardiography 2018 08 12;35(8):1116-1123. Epub 2018 Apr 12.

Department of Public Health and Clinical Medicine, Umea University and Heart Centre, Umea, Sweden.

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.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/echo.13891DOI Listing
August 2018
-->