| 1. |
- Broberg, Olof, et al.
(författare)
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Ceramides : a potential cardiovascular biomarker in young adult childhood cancer survivors?
- 2024
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Ingår i: European Heart Journal Open. - 2752-4191. ; 4:2
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Tidskriftsartikel (refereegranskat)abstract
- Aims The aim of this study was to investigate circulating ceramides involved in cardiovascular disease (CVD) in young adult childhood cancer survivors (CCS) and their correlations to previously reported adverse cardiovascular changes in this cohort. Methods Fifty-seven CCS and 53 healthy controls (age 20-30 years) were studied. Plasma long-chain ceramides, known to be cardi- and results otoxic (C16:0, C18:0, C24:0, and C24:1), were analysed by mass spectrometry. The coronary event risk test 2 (CERT2) score was calculated from the ceramide data. Cardiac and carotid artery ultrasound data and lipid data available from previous studies of this cohort were used to study partial correlations with ceramide and CERT2 score data. All four analysed ceramides were elevated in CCS compared with controls (P ≤ 0.012). The greatest difference was noted for C18:0, which was 33% higher in CCS compared with controls adjusted for sex, age, and body mass index (BMI) (P < 0.001). The CERT2 score was higher in CCS compared with controls (P < 0.001). In the CCS group, 35% had a high to very high CERT2 score (7-12) when compared with 9% in the control group (P < 0.001). The CCS subgroup with a CERT2 score ≥ 7 had higher heart rate, systolic blood pressure, and higher levels of apolipoprotein B compared with CCS with a CERT2 score < 6 (P ≤ 0.011). When adjusted for age, sex, and BMI, CERT2 score was significantly correlated with arterial stiffness, growth hormone, and cranial radiotherapy (P < 0.044). Conclusion Ceramides could be important biomarkers in understanding the pathophysiology of CVD and in predicting CVD disease risk in young adult CCS.
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| 2. |
- Broberg, Olof, et al.
(författare)
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Characterization of Cardiac, Vascular, and Metabolic Changes in Young Childhood Cancer Survivors
- 2021
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Ingår i: Frontiers in Pediatrics. - : Frontiers Media SA. - 2296-2360. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Background: Childhood cancer survivors (CCS) are at an increased risk for cardiovascular diseases (CVD). It was the primary aim of this study to determine different measures of cardiac, carotid, lipid, and apolipoprotein status in young adult CCS and in healthy controls. Methods: Cardiac and common carotid artery (CCA) structure and function were measured by ultrasonography. Lipids and apolipoproteins were measured in the blood. Peripheral arterial endothelial vasomotor function was assessed by measuring digital reactive hyperemia index (PAT-RHI) using the Endo-PAT 2000. Results: Fifty-three CCS (20-30 years, 35 men) and 53 sex-matched controls were studied. The CCS cohort was divided by the median dose of anthracyclines into a low anthracycline dose (LAD) group (50-197 mg/m2, n = 26) and a high anthracycline dose (HAD) group (200-486 mg/m2, n = 27). Carotid distensibility index (DI) and endothelial function determined by PAT-RHI were both lower in the CCS groups compared with controls (p < 0.05 and p = 0.02). There was no difference in carotid intima media thickness. Atherogenic apolipoprotein-B (Apo-B) and the ratio between Apo-B and Apoliprotein-A1 (Apo-A1) were higher in the HAD group compared with controls (p < 0.01). Apo-B/Apo-A1-ratio was over reference limit in 29.6% of the HAD group, in 15.4% of LAD group, and in 7.5% of controls (p = 0.03). Measured lipid markers (low density lipoprotein and total cholesterol and triglycerides) were higher in both CCS groups compared with controls (p < 0.05). Systolic and diastolic function were measurably decreased in the HAD group, as evidenced by lower EF (p < 0.001) and lower é-wave (p < 0.005) compared with controls. CCA DI correlated with Apo-B/Apo-A1-ratio and Apo-A1. Follow-up time after treatment correlated with decreased left ventricular ejection fraction (p = 0.001). Conclusion: Young asymptomatic CCS exhibit cardiac, vascular, lipid, and apolipoprotein changes that could account for increased risk for CVD later in life. These findings emphasize the importance of cardiometabolic monitoring even in young CCS.
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| 3. |
- Broberg, Olof, et al.
(författare)
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Circulating leptin is associated with adverse vascular changes in young adult survivors of childhood cancer
- 2024
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Ingår i: Cardiology in the Young. - 1047-9511 .- 1467-1107.
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Tidskriftsartikel (refereegranskat)abstract
- INTRODUCTION: Proteomics may help discover novel biomarkers and underlying mechanisms for cardiovascular disease. This could be useful for childhood cancer survivors as they show an increased risk of cardiovascular disease. The aim of this study was to investigate circulating cardiovascular proteins in young adult survivors of childhood cancer and their relationship to previously reported subclinical cardiovascular disease.METHODS: Ninety-two cardiovascular proteins were measured in 57 childhood cancer survivors and in 52 controls. For proteins that were significantly different between childhood cancer survivors and controls, we performed correlations between protein levels and measures of peripheral arterial stiffness (carotid distensibility and stiffness index, and augmentation index) and endothelial dysfunction (reactive hyperemia index).RESULTS: Leptin was significantly higher in childhood cancer survivors compared to controls (normalized protein expression units: childhood cancer survivors 6.4 (1.5) versus 5.1 (1.7), p < 0.0000001) after taking multiple tests into account. Kidney injury molecule-1, MER proto-oncogene tyrosine kinase, selectin P ligand, decorin, alpha-1-microglobulin/bikunin precursor protein, and pentraxin 3 showed a trend towards group differences (p < 0.05). Among childhood cancer survivors, leptin was associated with anthracycline treatment after adjustment for age, sex, and body mass index (p < 0.0001). Higher leptin correlated with lower carotid distensibility after adjustment for age, sex, body mass index, and treatments with radiotherapy and anthracyclines (p = 0.005).CONCLUSION: This proteomics approach identified that leptin is higher in young asymptomatic adult survivors of childhood cancer than in healthy controls and is associated with adverse vascular changes. This could indicate a role for leptin in driving the cardiovascular disease burden in this population.
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| 4. |
- de Simone, Giovanni, et al.
(författare)
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Hypertension in children and adolescents. : A consensus document from ESC Council on Hypertension, European Association of Preventive Cardiology, European Association of Cardiovascular Imaging, Association of Cardiovascular Nursing & Allied Professions, ESC Council for Cardiology Practice and Association for European Paediatric and Congenital Cardiology
- 2022
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Ingår i: European heart journal. - : Oxford University Press (OUP). - 1522-9645 .- 0195-668X. ; 43:35, s. 3290-3301
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Tidskriftsartikel (refereegranskat)abstract
- Definition and management of arterial hypertension in children and adolescents are uncertain, due to different positions of current guidelines. The European Society of Cardiology task-force, constituted by Associations and Councils with interest in arterial hypertension, has reviewed current literature and evidence, to produce a Consensus Document focused on aspects of hypertension in the age range of 6-16 years, including definition, methods of measurement of blood pressure, clinical evaluation, assessment of hypertension-mediated target organ damage, evaluation of possible vascular, renal and hormonal causes, assessment and management of concomitant risk factors with specific attention for obesity, and anti-hypertensive strategies, especially focused on life-style modifications. The Consensus Panel also suggests aspects that should be studied with high priority, including generation of multi-ethnic sex, age and height specific European normative tables, implementation of randomized clinical trials on different diagnostic and therapeutic aspects, and long-term cohort studies to link with adult cardiovascular risk. Finally, suggestions for the successful implementation of the contents of the present Consensus document are also given.
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| 5. |
- Elkinany, Sherif, et al.
(författare)
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Is Aortic Z-score an Appropriate Index of Beneficial Drug Effect in Clinical Trials in Aortic Aneurysm Disease?
- 2021
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 143
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Tidskriftsartikel (refereegranskat)abstract
- Aortic Z-score (Z-score) is utilized in clinical trials to monitor the effect of medications on aortic dilation rate in Marfan (MFS) patients. Z-scores are reported in relation to body surface area and therefore are a function of height and weight. However, an information void exists regarding natural, non-pharmacological changes in Z-scores as children age. We had concerns that Z-score decrease attributed to “therapeutic” effects of investigational drugs for Marfan disease connective tissue diseases might simply reflect normal changes (“filling out” of body contour) as children age. This investigation studies natural changes with age in Z-score in normal and untreated MFS children, teasing out normal effects that might erroneously be attributed to drug benefit. (1) We first compared body mass index (BMI) and Z-scores (Boston Children's Hospital calculator) in 361 children with “normal” single echo exams in four age ranges (0 to 1, 5 to 7, 10 to 12, 15 to 18 years). Regression analysis revealed that aging itself decreases ascending Z-score, but not root Z-score, and that increase in BMI with aging underlies the decreased Z-scores. (2) Next, we examined Z-score findings in both “normal” and Marfan children (all pharmacologically untreated) as determined on sequential echo exams over time. Of 27 children without aortic disease with sequential echos, 19 (70%) showed a natural decrease in root Z-score and 24 (89%) showed a natural decrease in ascending Z- score, over time. Of 25 untreated MFS children with sequential echos, 12 (40%) showed a natural decrease in root Z-score and 10 (33%) showed a natural decrease in ascending Z-score. Thus, Z-score is over time affected by natural factors even in the absence of any aneurysmal pathology or medical intervention. Specifically, Z-score decreases spontaneously as a natural phenomenon as children age and with fill out their BMI. Untreated Marfan patients often showed a spontaneous decrease in Z-score. In clinical drug trials in aneurysm disease, decreasing Z-score has been interpreted as a sign of beneficial drug effect. These data put such conclusions into doubt.
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| 6. |
- Ernstsson, Julia, et al.
(författare)
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Validation of smartwatch electrocardiogram intervals in children compared to standard 12 lead electrocardiograms
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Ingår i: European Journal of Pediatrics. - 1432-1076.
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Tidskriftsartikel (refereegranskat)abstract
- UNLABELLED: Lay people are now able to obtain one-lead electrocardiograms (ECG) using smartwatches, which facilitates documentation of arrhythmias. The accuracy of smartwatch derived ECG intervals has not been validated in children though. Home-based monitoring of ECG intervals using a smartwatch could improve monitoring of children, e.g. when taking QTc prolonging medications. The aim of this study was to validate the ECG intervals measured by smartwatch in comparison to standard 12-lead ECGs in children and adolescents. Prospective study of children (age 5-17 years) at the outpatient clinic of a national pediatric heart center. Patients underwent a smartwatch ECG (ScanWatch, Withings) and a simultaneous standard 12-lead ECG. ECG intervals were measured both automatically and manually from the smartwatch ECG and the 12-lead ECG. Intraclass correlation coefficients and Bland-Altman plots were performed. 100 patients (54% male, median age 12.9 (IQR 8.7-15.6) were enrolled. The ICC calculated from the automated smartwatch and automated 12-lead ECG were excellent for heart rate (ICC 0.97, p < 0.001), good for the PR and QT intervals (ICC 0.86 and 0.8, p < 0.001), and moderate for the QRS duration and QTc interval (ICC 0.7 and 0.53, p < 0.001). When using manual measurements for the smartwatch ECG, validity was improved for the PR interval (ICC 0.93, p < 0.001), QRS duration (ICC 0.92, p < 0.001), QT (ICC 0.95, p < 0.001) and QTc interval (ICC 0.84, p < 0.001).CONCLUSION: Automated smartwatch intervals are most reliable measuring the heart rate. The automated smartwatch QTc intervals are less reliable, but this may be improved by manual measurements.WHAT IS KNOWN: In adults, smartwatch derived ECG intervals measured manually have previously been shown to be accurate, though agreement for automated QTc may be fair.WHAT IS NEW: In children, automated smartwatch QTc intervals are less reliable than RR, PR, QRS and uncorrected QT interval. Accuracy of the QTc can be improved by peroforming manual measurements.
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| 7. |
- Fricke, Katrin, et al.
(författare)
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Fetal cardiac magnetic resonance imaging of the descending aorta in suspected left-sided cardiac obstructions
- 2023
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Ingår i: Frontiers in Cardiovascular Medicine. - 2297-055X. ; 10, s. 01-10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Severe left-sided cardiac obstructions are associated with high morbidity and mortality if not detected in time. The correct prenatal diagnosis of coarctation of the aorta (CoA) is difficult. Fetal cardiac magnetic resonance imaging (CMR) may improve the prenatal diagnosis of complex congenital heart defects. Flow measurements in the ascending aorta could aid in predicting postnatal CoA, but its accurate visualization is challenging.Objectives: To compare the flow in the descending aorta (DAo) and umbilical vein (UV) in fetuses with suspected left-sided cardiac obstructions with and without the need for postnatal intervention and healthy controls by fetal phase-contrast CMR flow. A second objective was to determine if adding fetal CMR to echocardiography (echo) improves the fetal CoA diagnosis.Methods: Prospective fetal CMR phase-contrast flow in the DAo and UV and echo studies were conducted between 2017 and 2022.Results: A total of 46 fetuses with suspected left-sided cardiac obstructions [11 hypoplastic left heart syndrome (HLHS), five critical aortic stenosis (cAS), and 30 CoA] and five controls were included. Neonatal interventions for left-sided cardiac obstructions (n = 23) or comfort care (n = 1 with HLHS) were pursued in all 16 fetuses with suspected HLHS or cAS and in eight (27%) fetuses with true CoA. DAo or UV flow was not different in fetuses with and without need of intervention. However, DAo and UV flows were lower in fetuses with either retrograde isthmic systolic flow [DAo flow 253 (72) vs. 261 (97) ml/kg/min, p = 0.035; UV flow 113 (75) vs. 161 (81) ml/kg/min, p = 0.04] or with suspected CoA and restrictive atrial septum [DAo flow 200 (71) vs. 268 (94) ml/kg/min, p = 0.04; UV flow 89 vs. 159 (76) ml/kg/min, p = 0.04] as well as in those without these changes. Adding fetal CMR to fetal echo predictors for postnatal CoA did not improve the diagnosis of CoA.Conclusion: Fetal CMR-derived DAo and UV flow measurements do not improve the prenatal diagnosis of left-sided cardiac obstructions, but they could be important in identifying fetuses with a more severe decrease in blood flow across the left side of the heart. The physiological explanation may be a markedly decreased left ventricular cardiac output with subsequent retrograde systolic isthmic flow and decreased total DAo flow.
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| 8. |
- Fricke, Katrin, et al.
(författare)
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Impact of Left Ventricular Morphology on Adverse Outcomes Following Stage 1 Palliation for Hypoplastic Left Heart Syndrome: 20 Years of National Data From Sweden
- 2022
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Ingår i: Journal of the American Heart Association. - : John Wiley & Sons. - 2047-9980. ; 11:7
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Tidskriftsartikel (refereegranskat)abstract
- 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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| 9. |
- Hidestrand, Pip, et al.
(författare)
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Impact of Underweight, Overweight, and Obesity on Health-Related Quality of Life in Children with Tetralogy of Fallot Variants
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Ingår i: Pediatric Cardiology. - 0172-0643.
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Tidskriftsartikel (refereegranskat)abstract
- Traditional cardiovascular risk factors put patients with congenital heart disease (CHD) at increased risk for cardiovascular morbidity and mortality. The aim of this study was to evaluate whether body mass index (BMI) is associated with health-related quality of life (HRQoL) in patients with variants of Tetralogy of Fallot (TOF). Patients and parents of children with variants of TOF–CHD were asked to fill out the PedsQL 4.0 questionnaire and provide weight and length. Patients were categorized into low, normal, and high BMI percentiles. Other demographic data were obtained from the Swedish national registry for congenital heart disease (SWEDCON). Statistical analyses included non-parametric Mann–Whitney U test, Fisher exact, and Chi-square tests. Eighty-five patients were included. Twelve were overweight or obese, 57 had a normal BMI, and 16 were underweight. There was a significant difference in age and gender between the groups. Comparing overweight/obese children to those with normal BMI, physical and social functioning were impaired, while emotional and school function were comparable between the groups. This applied to both child and parental assessment. When comparing underweight to normal weight children, school functioning assessed by the parent was the only domain significantly different from patients with a normal BMI. Children with variants of TOF and overweight/obesity have lower HRQoL, particularly in physical and social functioning, while underweight children may have impaired school functioning. We suggest that preventive measures aimed at maintaining a normal weight should be taken early in life to reduce long-term cardiovascular risk in the CHD population.
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| 10. |
- Hoffmann, Julia K., et al.
(författare)
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Who Still Gets Ligated? Reasons for Persistence of Surgical Ligation of the Patent Ductus Arteriosus Following Availability of Transcatheter Device Occlusion for Premature Neonates
- 2024
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Ingår i: Journal of cardiovascular development and disease. - 2308-3425. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- (1) Background: To identify reasons for the persistence of surgical ligation of the patent ductus arteriosus (PDA) in premature infants after the 2019 Food and Drug Administration (FDA) approval of transcatheter device closure; (2) Methods: We performed a 10-year (2014–2023) single-institution retrospective study of premature infants (<37 weeks) and compared clinical characteristics and neonatal morbidities between neonates that underwent surgical ligation before (epoch 1) and after (epoch 2) FDA approval of transcatheter closure; (3) Results: We identified 120 premature infants that underwent surgical ligation (n = 94 before, n = 26 after FDA approval). Unfavorable PDA morphology, active infection, and recent abdominal pathology were the most common reasons for surgical ligation over device occlusion in epoch 2. There were no differences in demographics, age at closure, or outcomes between infants who received surgical ligation in the two epochs; (4) Conclusions: Despite increasing trends for transcatheter PDA closure in premature infants, surgical ligation persists due to unfavorable ductal morphology, active infection, or abdominal pathology.
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