Cardiac dysfunction during exercise in young adults with bronchopulmonary dysplasia.

Background: Worldwide, 1-2% of children are born premature and at risk for developing bronchopulmonary dysplasia (BPD). Preterm-born adults are at risk for early cardiovascular disease. The role of BPD is unclear. This study aims to examine cardiorespiratory function during submaximal exercise in young adult survivors of extreme prematurity, with or without BPD. Methods: 40 preterm-born young adults, 20 with BPD (median gestational age 27 weeks, interquartile range (IQR) 26-28 weeks) and 20 without BPD (median gestational age 28 weeks, IQR 27-29 weeks) were prospectively compared to age-matched at term-born adults (median gestational age 39 weeks, IQR 38-40 weeks). Participants underwent exercise testing and cardiovascular magnetic resonance with submaximal exercise. Results: Resting heart rate in BPD subjects was higher than in at term-born subjects (69±10 mL versus 61±7 mL, p=0.01). Peak oxygen uptake during maximal cardiopulmonary exercise testing was decreased in BPD subjects (91±18% versus 106±17% of predicted, p=0.01). In BPD subjects, cardiac stroke volume change with exercise was impaired compared to at term-born subjects (11±13% versus 25±10%; p<0.001). With exercise, left ventricular end-diastolic volume decreased more in preterm-born subjects with versus without BPD (-10±8% versus -3±8%; p=0.01) and compared to at term-born subjects (0±5%; p<0.001). Exploratory data analysis revealed that exercise stroke volume and end-diastolic volume change were inversely correlated with oxygen dependency in those born prematurely. Conclusions: In preterm-born young adults, particularly those with BPD, resting cardiac function, exercise performance and cardiac response to exercise is impaired compared to controls. Exercise cardiovascular magnetic resonance may reveal an important predisposition for heart disease later in life.

The right ventricle in tetralogy of Fallot: adaptation to sequential loading.

Right ventricular dysfunction is a major determinant of outcome in patients with complex congenital heart disease, as in tetralogy of Fallot. In these patients, right ventricular dysfunction emerges after initial pressure overload and hypoxemia, which is followed by chronic volume overload due to pulmonary regurgitation after corrective surgery. Myocardial adaptation and the transition to right ventricular failure remain poorly understood. Combining insights from clinical and experimental physiology and myocardial (tissue) data has identified a disease phenotype with important distinctions from other types of heart failure. This phenotype of the right ventricle in tetralogy of Fallot can be described as a syndrome of dysfunctional characteristics affecting both contraction and filling. These characteristics are the end result of several adaptation pathways of the cardiomyocytes, myocardial vasculature and extracellular matrix. As long as the long-term outcome of surgical correction of tetralogy of Fallot remains suboptimal, other treatment strategies need to be explored. Novel insights in failure of adaptation and the role of cardiomyocyte proliferation might provide targets for treatment of the (dysfunctional) right ventricle under stress.

Multivendor Evaluation of Automated MRI Postprocessing of Biventricular Size and Function for Children With and Without Congenital Heart Defects.

BACKGROUND: Manually segmenting cardiac structures is time-consuming and produces variability in MRI assessments. Automated segmentation could solve this. However, current software is developed for adults without congenital heart defects (CHD). PURPOSE: To evaluate automated segmentation of left ventricle (LV) and right ventricle (RV) for pediatric MRI studies. STUDY TYPE: Retrospective comparative study. POPULATION: Twenty children per group of: healthy children, LV-CHD, tetralogy of Fallot (ToF), and univentricular CHD, aged 11.7 [8.9-16.0], 14.2 [10.6-15.7], 14.6 [11.6-16.4], and 12.2 [10.2-14.9] years, respectively. SEQUENCE/FIELD STRENGTH: Balanced steady-state free precession at 1.5 T. ASSESSMENT: Biventricular volumes and masses were calculated from a short-axis stack of images, which were segmented manually and using two fully automated software suites (Medis Suite 3.2, Medis, Leiden, the Netherlands and SuiteHeart 5.0, Neosoft LLC, Pewaukee, USA). Fully automated segmentations were manually adjusted to provide two further sets of segmentations. Fully automated and adjusted automated segmentation were compared to manual segmentation. Segmentation times and reproducibility for each method were assessed. STATISTICAL TESTS: Bland Altman analysis and intraclass correlation coefficients (ICC) were used to compare volumes and masses between methods. Postprocessing times were compared by paired t-tests. RESULTS: Fully automated methods provided good segmentation (ICC > 0.90 compared to manual segmentation) for the LV in the healthy and left-sided CHD groups (eg LV-EDV difference for healthy children 1.4 ± 11.5 mL, ICC: 0.97, for Medis and 3.0 ± 12.2 mL, ICC: 0.96 for SuiteHeart). Both automated methods gave larger errors (ICC: 0.62-0.94) for the RV in these populations, and for all structures in the ToF and univentricular CHD groups. Adjusted automated segmentation agreed well with manual segmentation (ICC: 0.71-1.00), improved reproducibility and reduced segmentation time in all patient groups, compared to manual segmentation. DATA CONCLUSION: Fully automated segmentation eliminates observer variability but may produce large errors compared to manual segmentation. Manual adjustments reduce these errors, improve reproducibility, and reduce postprocessing times compared to manual segmentation. Adjusted automated segmentation is reasonable in children with and without CHD. EVIDENCE LEVEL: 3. TECHNICAL EFFICACY: Stage 2.

Exercise capacity in a cohort of children with congenital heart disease.

In patients with congenital heart disease (CHD), reduced exercise capacity can be a predictor for late complications and may be used to guide interventions. Yet, the interpretation of exercise capacity is challenged by changes in body composition during growth. Our aim was to create an overview of disease-specific exercise capacity in children with CHD. We performed a multicentre retrospective study of exercise capacity of CHD patients, aged 6-18 years, tested between January 2001 and October 2018. Sex-specific distribution graphs were made using the LMS method and height to relate to body size. We included all CHD with N > 50, including severe defects (e.g., univentricular heart, tetralogy of Fallot) and "simple" lesions as ventricular septum defect and atrial septum defect. We included 1383 tests of 1208 individual patients for analysis. The peak oxygen uptake (VO2peak, 37.3 ml/min/kg (25th-75th percentile 31.3-43.8)) varied between specific defects; patients with univentricular hearts had lower VO2peak compared with other CHD. All groups had lower VO2peak compared to healthy Dutch children. Males had higher VO2peak, Wpeak and O2pulsepeak than females. Sex- and disease-specific distribution graphs for VO2peak, Wpeak and O2pulsepeak showed increase in variation with increase in height.   Conclusion: Disease-specific distribution graphs for exercise capacity in children with CHD from a large multicentre cohort demonstrated varying degrees of reduced VO2peak and Wpeak. The distribution graphs can be used in the structured follow-up of patients with CHD to predict outcome and identify patients at risk. What is Known: • Children with congenital heart disease (COnHD) are at risk to develop heart failure, arrhytmia's and other complications. Exercise capacity may be an important predictor for outcome in children with ConHD. In children, the interpretation of exercise capacity poses an additional challenge related to physical changes during growth. What is New: • In this report of a multi-center cohort >1300 childrewn with ConHD, we related the changes in exercise capacity to length. We demonstrated that exercise capacity was reduced as compared with healthy children and we observed variation between disease groups. Patients with a univentricular circulation (Fontan) had worse exercise capacity. We constructed disease specific charts of development of exercise capacity throughout childhood, accessible via a web-site. These graphs may help practitioner to guide children with ConHD.

Associations between blood biomarkers, cardiac function and adverse outcome in a young tetralogy of Fallot cohort.

BACKGROUND: To determine the potential prognostic value and clinical correlations of blood biomarkers in a cohort of patients with Tetralogy of Fallot (TOF). METHODS: In the setting of multicenter prospective research studies TOF patients underwent blood sampling, cardiopulmonary exercise testing and low-dose dobutamine stress cardiac magnetic resonance (CMR) imaging. In the blood sample NT-proBNP, GDF-15, Galectin-3, ST-2, DLK-1, FABP4, IGFBP-1, IGFBP-7, MMP-2, and vWF were assessed. During subsequent follow-up, patients were evaluated for reaching the study endpoint (cardiac death, arrhythmia-related hospitalization or cardioversion/ablation, VO2 max ≤65% of predicted). Regression analysis was used to explore the correlation between blood biomarkers (corrected for age and gender) and other clinical parameters. The potential predictive value of blood biomarkers and events were assessed with Kaplan-Meier analysis and Cox proportional hazard analysis. RESULTS: We included 137 Fallot patients, median age 19.2 (interquartile range: 14.6-25.7) years, median age at TOF-repair 0.9 (0.5-1.9) years. After a median follow-up of 8.7 (6.3-10.7) years, 20 (14.6%) patients reached the composite endpoint. In a multivariable cox-regression analysis corrected for age at study baseline, elevated IGFBP-7 and MMP-2 levels were associated with the composite endpoint. We also noted a correlation between DLK-1 and relative change in right ventricular end systolic volume during dobutamine stress CMR (ß = -0.27, p = 0.010), a correlation between FABP4 and Max VO2 (ß = -0.41, p ≤0.001 and between MMP-2 and tricuspid valve E/A ratio (ß = -0.15, p = 0.037). CONCLUSIONS: IGFBP-7, MMP-2 and DLK-1 levels are related to cardiac function and long-term outcome in TOF patients.

Ethnic differences in childhood right and left cardiac structure and function assessed by cardiac magnetic resonance imaging.

Ethnic differences in cardiovascular risk factors and disease are well-known and may originate in early-life. We examined the ethnic differences in cardiac structure and function in children using cardiac magnetic resonance imaging in a European migrant population, and whether any difference was explained by early life factors. We used a prospective population-based cohort study among 2317 children in Rotterdam, the Netherlands. We compared children from Dutch (73%), Cape Verdean (3.5%), Dutch Antillean (3.3%), Moroccan (6.1%), Surinamese-Creoles (3.9%), Surinamese-Hindustani (3.4%), and Turkish (6.4%) background. Main outcomes were cMRI-measured cardiac structures and function. Cardiac outcomes were standardized on body surface area. Cape Verdean, Surinamese-Hindustani, and Turkish children had smaller right ventricular end-diastolic volume and left ventricular end-diastolic volume relative to their body size than Dutch children (p < 0.05). These results were not fully explained by fetal and childhood factors. Right ventricular ejection fraction and left ventricular ejection fraction did not differ between ethnicities after adjustment for fetal and childhood factors.Conclusion: Right ventricular end-diastolic volume and left ventricular end-diastolic volume differ between ethnic subgroups in childhood, without affecting ejection fraction. Follow-up studies are needed to investigate whether these differences lead to ethnic differences in cardiac disease in adulthood. What is Known: • Ethnic differences in cardiovascular risk factors and disease are well-known and may originate in early-life. • The prevalence of cardiovascular disease differs between ethnic groups. What is New: • We examined ethnic differences in left and right cardiac structure and function in children using cMRI. • Right and left cardiac dimensions differ between ethnic groups in childhood and are only partly explained by fetal and childhood factors.