Efficacy of interdisciplinary rehabilitation in child cancer survivors: Impact on physical fitness, fatigue and body composition after 1-year follow-up.

OBJECTIVE: Childhood cancer survivors experience reduced physical activity level, participation as well as health-related quality of life. This prospective, pre-/post-intervention and follow-up cohort study aims to determine the efficacy of an interdisciplinary rehabilitation on improving physical fitness, fatigue and body composition. METHODS: A total of 24 childhood cancer survivors (mean age: 12.15 years ± 3.2; 14 females; 10 males) were recruited 6 months after medical treatment and received a 4-month interdisciplinary intervention. Cardiorespiratory fitness (PredVO2peak and PredLoadmax ), body composition (dry lean weight) and quality of life (general fatigue) were assessed at baseline, post-intervention and 1-year follow-up. Linear mixed models were used to analyse data. RESULTS: Linear mixed modelling revealed a significant main effect of time on predicted maximal load (F = 13.189, df = 36.179, p < 0.001), dry lean weight (F = 64.813, df = 37.019, p < 0.001) but also significant improvement of general fatigue score (-9.039 ± 4.300, 95% CI -17.741 to -0.336, p = 0.042), indicating a decline in general fatigue. CONCLUSION: With emerging evidence that physical activity is safe and feasible, together with increasing numbers of childhood cancer survivors at risk for long-term chronic co-morbidities, this study advocates for better access to interdisciplinary rehabilitation programmes in order to improve their physical condition and their body composition and reduce fatigue.

Paediatric subaortic stenosis: long-term outcome and risk factors for reoperation.

OBJECTIVES: Surgical repair of subaortic stenosis (SAS) is associated with a substantial reoperation risk. We aimed to identify risk factors for reintervention in relation to discrete and tunnel-type SAS morphology. METHODS: Single-centre retrospective study of paediatric SAS diagnosed between 1992 and 2017. Multivariable Cox regression analysis was performed to identify reintervention risk factors. RESULTS: Eighty-five children [median age 2.5 (0.7-6.5) years at diagnosis] with a median follow-up of 10.1 (5.5-16.4) years were included. Surgery was executed in 83% (n = 71). Freedom from reoperation was 88 ± 5% at 5 years and 82 ± 6% at 10 years for discrete SAS, compared to, respectively, 33 ± 16% and 17 ± 14% for tunnel-type SAS (log-rank P < 0.001). Independent risk factors for reintervention were a postoperative gradient >20 mmHg [hazard ratio (HR) 6.56, 95% confidence interval (CI) 1.41-24.1; P = 0.005], tunnel-type SAS (HR 7.46, 95% CI 2.48-22.49; P < 0.001), aortic annulus z-score <-2 (HR 11.07, 95% CI 3.03-40.47; P < 0.001) and age at intervention <2 years (HR 3.24, 95% CI 1.09-9.86; P = 0.035). Addition of septal myectomy at initial intervention was not associated with lesser reintervention. Fourteen children with a lower left ventricular outflow tract (LVOT) gradient (P < 0.001) and older age at diagnosis (P = 0.024) were followed expectatively. CONCLUSIONS: Children with SAS remain at risk for reintervention, despite initially effective LVOT relief. Regardless of SAS morphology, age <2 years at first intervention, a postoperative gradient >20 mmHg and presence of a hypoplastic aortic annulus are independent risk factors for reintervention. More extensive LVOT surgery might be considered at an earlier stage in these children. SAS presenting in older children with a low LVOT gradient at diagnosis shows little progression, justifying an expectative approach.

Analysis of the recovery phase after maximal exercise in children with repaired tetralogy of Fallot and the relationship with ventricular function.

BACKGROUND: Few studies demonstrate delayed recovery after exercise in children and adults with heart disease. We assess the recovery patterns of gas exchange parameters and heart rate (HR) in children with repaired Tetralogy of Fallot (rToF) compared to healthy peers and investigate the correlation with ventricular function and QRS duration. METHODS: 45 children after rToF and 45 controls performed a maximal incremental cardiopulmonary exercise test. In the subsequent recovery period, patterns of VO2, VCO2 and HR were analysed. Half-life time (T1/2) of the exponential decay and drop per minute (Recmin) were compared between groups. In the rToF group, correlations were examined between the recovery parameters and QRS-duration and ventricular function, described by fractional shortening (FS) and tricuspid annular plane systolic excursion (TAPSE) measured at baseline prior to exercise. RESULTS: Recovery of VO2 and VCO2 was delayed in rToF patients, half-life time values were higher compared to controls (T1/2VO2 52.51 ±11.29 s vs. 44.31 ± 10.47 s; p = 0.001 and T1/2VCO2 68.28 ± 13.84 s vs. 59.41 ± 12.06 s; p = 0.002) and percentage drop from maximal value was slower at each minute of recovery (p<0.05). Correlations were found with FS (T1/2VO2: r = -0.517; p<0.001; Rec1minVO2: r = -0.636, p<0.001; Rec1minVCO2: r = -0.373, p = 0.012) and TAPSE (T1/2VO2: r = -0.505; p<0.001; Rec1minVO2: r = -0.566, p<0.001; T1/2VCO2: r = -0.466; p = 0.001; Rec1minVCO2: r = -0.507, p<0.001), not with QRS-duration. No difference was found in HR recovery between patients and controls. CONCLUSIONS: Children after rToF show a delayed gas exchange recovery after exercise. This delay correlates to ventricular function, demonstrating its importance in recovery after physical activity.

A new dimension in patent foramen ovale size estimation.

BACKGROUND: Detailed multidimensional assessment of patent foramen ovale (PFO) size with transesophageal echocardiography (TOE) may help to determine PFO pathogenicity in cryptogenic stroke patients. We explored the potential additive value of Live xPlane and three-dimensional (3D) TOE anatomical PFO sizing techniques. METHODS: Imaging data of 45 patients who underwent a 3D TOE-assisted percutaneous PFO closure were studied. The two-dimensional (2D) PFO separation distance and right-to-left (RL) contrast shunt magnitude were assessed on preprocedural TOE recordings. Peri-procedural measurements of the triangular anatomical PFO opening (base, height, and area) were performed after positioning of a stiff guidewire (SW) through the PFO, using Live xPlane imaging and 3D Zoom mode. RESULTS: The PFO SW base appeared on average 5 times larger than the preprocedural 2D PFO separation (median difference [IQR] = 13[5] mm; P < .001). For a same PFO separation, the width of the PFO base may vary significantly. The PFO SW base was significantly larger in patients with a large versus a small-to-moderate PFO RL contrast shunt (18 vs 15 mm; P = .007) and in those with a spontaneous versus a provoked shunt (18 vs 14 mm; P = .003). CONCLUSION: Live xPlane and 3D Zoom TOE allow peri-procedural measurement of the largest dimension of a PFO, which is the PFO base. Patients with a large or spontaneous RL contrast shunt appear to have a larger PFO base. The anatomical PFO base dimension may be taken into account for optimization of device and patient selection strategies.

Echocardiography during submaximal isometric exercise in children with repaired coarctation of the aorta compared with controls.

Objective: Patients with repaired coarctation (RCoA) remain at higher risk of cardiac dysfunction, initially often only detected during exercise. In this study, haemodynamics of isometric handgrip (HG) and bicycle ergometry (BE) were compared in patients with RCoA and matched controls (MCs). Methods: Case-control study of 19 children with RCoA (mean age 12.9±2.3 years; mean age of repair 7 months) compared with 20 MC. HG with echocardiography followed by BE was performed in both groups. Results: During HG (blood pressure) BP increased from 114±11/64±4 mm Hg to 132±14/79±7 mm Hg, without significant differences. During HG as well as BE, HR increased less in patients with RCoA. There were no significant differences in (left ventricle) LV dimensions or LV mass.The RCoA group had diastolic dysfunction: both at rest and during HG they had significantly higher transmitral E and A velocities and lower tissue Doppler E' and A' velocities. E/E' was higher, reaching statistical significance during HG (p<0001).Conventional parameters of systolic function (FS and EF) were similar at rest and HG. More sensitive tissue Doppler S' was significantly lower at rest in CoA subjects (5.1±1.5 cm/s vs 6.5±1±1 cm/s; p<0.01), decreasing further during HG by 5% in the CoA group (NS) while unchanged in controls. Conclusions: We provide first evidence that HG with echocardiography is feasible, easy and patient-friendly. A decreased systolic (tissue Doppler) and impaired diastolic LV function was measured in the RCoA group, a difference that tended to increase during HG.

Differences in cerebral and muscle oxygenation patterns during exercise in children with univentricular heart after Fontan operation compared to healthy peers.

BACKGROUND: We assess whether the lower exercise tolerance in children with univentricular heart (UVH) after Fontan operation is associated with altered peripheral muscular and cerebral tissue oxygenation. METHODS: 18 children with UVH and 20 healthy subjects performed an incremental ramp exercise test. Changes in the cerebral and muscular pattern of oxygenated (O2Hb) and deoxygenated hemoglobin (HHb) and local tissue oxygenation (TOI) were analyzed by means of Near Infrared Spectroscopy (NIRS). Correlations between arterial saturation during exercise and tissue oxygenation were evaluated. RESULTS: In UVH, maximal oxygen consumption (VO2peak/kg, 28.9 ±â€¯7.9 vs. 46.3 ±â€¯11.9 ml/min/kg, P < 0.001), heart rate (HRpeak, 168 ±â€¯13 vs. 193 ±â€¯12 bpm, P < 0.001) and load (Ppeak, 73 ±â€¯19 vs. 133 ±â€¯68 W, P < 0.001) were lower, VE/VCO2 slope was higher (34.5 ±â€¯5.9 vs. 27.1 ±â€¯3.9, P < 0.001). A faster and steeper course up to the same level of HHb and absent increase in O2Hb was seen at cerebral level in UVH; tissue oxygenation index (TOI) demonstrated a steady decrease from the start of exercise. At the muscular level, HHb curve has a similar pattern compared to controls, with an early cessation. O2Hb has a similar pattern, but with early discontinuation at a higher O2Hb-level. Muscular TOI has the same course throughout exercise, starting from a lower level. Lower arterial saturation and higher age correlated with lower VO2peak; higher amplitude of muscular TOI and lower amplitude cerebral TOI correlated with higher VO2peak. CONCLUSION: Children after Fontan procedure have different oxygenation mechanisms at muscular and cerebral level. This reflects a different balance between O2 supply to O2 demand which might contribute to the reduced exercise tolerance in this patient population.

Different Patterns of Cerebral and Muscular Tissue Oxygenation 10 Years After Coarctation Repair.

The purpose of this study was to assess whether the lower exercise tolerance in children after coarctation repair is associated with alterations in peripheral tissue oxygenation during exercise. A total of 16 children after coarctation repair and 20 healthy control subjects performed an incremental ramp exercise test to exhaustion. Cerebral and locomotor muscle oxygenation were measured by means of near infrared spectroscopy. The responses of cerebral and muscle tissue oxygenation index (cTOI, mTOI), oxygenated (O2Hb), and deoxygenated hemoglobin (HHb) as a function of work rate were compared. Correlations between residual continuous wave Doppler gradients at rest, arm-leg blood pressure difference and local oxygenation responses were evaluated. Age, length, and weight was similar in both groups. Patients with aortic coarctation had lower peak power output (Ppeak) (72.3 ± 20.2% vs. 106 ± 18.7%, P < 0.001), VO2peak/kg (37.3 ± 9.1 vs. 44.2 ± 7.6 ml/kg, P = 0.019) and %VO2peak/kg (85.7 ± 21.9% vs. 112.1 ± 15.5%, P < 0.001). Cerebral O2Hb and HHb had a lower increase in patients vs. controls during exercise, with significant differences from 60 to 90% Ppeak (O2Hb) and 70% to 100% Ppeak (HHb). Muscle TOI was significantly lower in patients from 10 to 70% Ppeak and muscle HHb was significantly higher in patients vs. controls from 20 to 80% Ppeak. Muscle O2Hb was not different between both groups. There was a significant correlation between residual resting blood pressure gradient and Δmuscle HHb/ΔP at 10-20W and 20-30W (r = 0.40, P = 0.039 and r = 0.43, P = 0.034). Children after coarctation repair have different oxygenation responses at muscular and cerebral level. This reflects a different balance between O2 supply to O2 demand which might contribute to the reduced exercise tolerance in this patient population.

Evaluation of cardiopulmonary exercise testing, heart function, and quality of life in children after allogenic hematopoietic stem cell transplantation.

BACKGROUND: Physical fitness is an important determinant of quality of life (QOL) after hematopoietic stem cell transplantation. Cardiac function can influence exercise performance. The aim of this study was to assess these factors and their interrelationship. PROCEDURE: Children underwent cardiopulmonary exercise testing (CPET) at least 1 year after hematopoietic stem cell transplantation (HSCT) and were compared with healthy controls. Systolic and diastolic heart function and left ventricle (LV) wall dimensions were measured. Health-related QOL (HR-QOL) was evaluated using PedsQL questionnaires. RESULTS: Forty-three patients performed CPET (26 boys, 13.6 ± 3.4 years, weight 45.5 ± 13.3 kg, length 152.9 ± 17.5 cm, body surface area 1.35 ± 0.28). HSCT patients had lower maximal oxygen consumption (VO2peak/kg, 34.7 ± 8.4 vs 46.3 ± 7.1 mL/kg/min, P < 0.001), shorter exercise duration (9.1 ± 2.5 vs 12.9 ± 2.6 min, P < 0.001), and lower maximal load (%Ppeak 70.8 ± 19.7 vs 102.4% ± 15.9%, P < 0.001). Echocardiography demonstrated decreased interventricular septal wall thickness (interventricular septum in diastole [IVSd] Z-value -0.64 ± 0.69, P < 0.001), and more systolic (11% of patients) and diastolic dysfunction (high E/E' Z-value 1.06 ± 1.13, P < 0.001). LV dilatation correlates with VO2max/kg (r = -0.364, P = 0.017). HR-QOL showed lower overall and emotional functioning scores (respectively, P = 0.016 and P = 0.001). Patients after anthracycline therapy have the lowest maximal exercise performance, but have no difference in QOL. Diminished exercise performance is not encountered as a QOL limitation. Total body irradiation influences the domain of psychosocial functioning. CONCLUSIONS: LV (systolic and diastolic) and right ventricle dysfunctions justify the need for thorough cardiac follow-up in children after HSCT. Lower physical fitness levels and lower HR-QOL emphasize the importance of CPET and fitness programs.

Exercise performance and quality of life in children with cystic fibrosis and mildly impaired lung function: relation with antibiotic treatments and hospitalization.

This study evaluates the impact of antibiotic treatments and hospitalization on exercise performance and health-related quality of life (QOL) in children with mild cystic fibrosis (CF) lung disease. Forty-seven children between 7 and 17 years with mild CF underwent a maximal exercise test including spiro-ergometry and filled out a QOL-questionnaire (PedsQL™). Amount of antibiotic treatments (AB) and hospitalization days in the last 3 years were reviewed. FEV1% was mildly decreased (91.7 ± 17.9 L/min, p = 0.02). Maximal oxygen consumption (VO2max), test duration and anaerobic threshold were lower compared to a control population (VO2max% 94 ± 15 vs 103 ± 13, p = 0.009). FEV1% correlated with AB and hospitalization episodes in the last year and 3 years before testing, VO2max% only correlated with AB in the last 3 years. Domains of school functioning and emotional functioning were low. Children with higher VO2max% and less AB in the last 3 years had better physical health. Physical health and school functioning were negatively correlated with hospitalization days in the last year. CONCLUSION: Patients with mild CF lung disease have good exercise performance although still lower than the normal population. VO2max% is affected by number of antibiotic treatments over a longer period. There is an impact of hospitalization days on quality of life. What is Known: • Children with CF have lower exercise performance; there is an association between hospitalization frequency and exercise performance • Quality of life is diminished in children with CF and influenced by respiratory infections What is New: • Even patients with mild CF lung disease have lower maximal exercise performance (VO 2 max) and a lower anaerobic threshold; VO 2 max is lower in children who had more antibiotic treatments in the last 3 years • School and emotional functioning are diminished in children with mild CF lung disease; hospitalization is negatively correlated with school functioning and physical functioning.

Characterizing cerebral and locomotor muscle oxygenation to incremental ramp exercise in healthy children: relationship with pulmonary gas exchange.

AIMS: To characterize the oxygenation responses at cerebral and locomotor muscle level to incremental exercise in children and to assess the interrelationship with the pulmonary gas exchange responses. METHODS: Eighteen children (9 boys, 9 girls) (mean age 10.9 ± 1.0 years) performed incremental cycle ramp exercise to exhaustion. The concentration of cerebral and muscle oxygenated (O2Hb) and deoxygenated (HHb) hemoglobin (by means of near-infrared spectroscopy) and pulmonary gas exchange was recorded. Cerebral and muscle O2Hb and HHb values were expressed as functions of oxygen uptake (VO2) and breakpoints were detected by means of double linear model analysis. The respiratory compensation point (RCP) was determined. The breakpoints in cerebral and muscle O2Hb and HHb were compared and correlated to RCP. RESULTS: The subjects reached peak power output of 105 ± 18 W and VO2peak of 43.5 ± 7.0 ml min-1 kg-1. Cerebral O2Hb increased to an intensity of 89.4 ± 5.5 %VO2peak, where a breakpoint occurred at which cerebral O2Hb started to decrease. Cerebral HHb increased slightly to 88.1 ± 4.8 %VO2peak, at which the increase was accelerated. Muscle HHb increased to 90.5 ± 4.8 %VO2peak where a leveling-off occurred. RCP occurred at 89.3 ± 4.3 %VO2peak. The breakpoints and RCP did not differ significantly (P = 0.13) and were strongly correlated (r > 0.70, P < 0.05). There were no differences between boys and girls (P = 0.43) and there was no significant correlation with VO2peak (P > 0.05). CONCLUSIONS: It was shown that cerebral and muscle oxygenation responses undergo significant changes as work rate increases and show breakpoints in the ongoing response at high intensity (85-95 %VO2peak). These breakpoints are strongly interrelated and associated with changes in pulmonary gas exchange.

An integrated view on the oxygenation responses to incremental exercise at the brain, the locomotor and respiratory muscles.

In the past two decades oxygenation responses to incremental ramp exercise, measured non-invasively by means of near-infrared spectroscopy at different locations in the body, have advanced the insights on the underpinning mechanisms of the whole-body pulmonary oxygen uptake ([Formula: see text]) response. In healthy subjects the complex oxygenation responses at the level of locomotor and respiratory muscles, and brain were simplified and quantified by the detection of breakpoints as a deviation in the ongoing response pattern as work rate increases. These breakpoints were located in a narrow intensity range between 75 and 90 % of the maximal [Formula: see text] and were closely related to traditionally determined thresholds in pulmonary gas exchange (respiratory compensation point), blood lactate measurements (maximal lactate steady state), and critical power. Therefore, it has been assumed that these breakpoints in the oxygenation patterns at different sites in the body might be equivalent and could, therefore, be used interchangeably. In the present review the typical oxygenation responses (at locomotor and respiratory muscle level, and cerebral level) are described and a possible framework is provided showing the physiological events that might link the breakpoints at different body sites with the thresholds determined from pulmonary gas exchange and blood lactate measurements. However, despite a possible physiological association, several arguments prevent the current practical application of these breakpoints measured at a single site as markers of exercise intensity making it highly questionable whether measurements of the oxygenation response at one single site can be used as a reflection of whole-body responses to different exercise intensities.

Evaluation of Exercise Performance, Cardiac Function, and Quality of Life in Children After Liver Transplantation.

BACKGROUND: In children, after having liver transplantation (LT), it is important to assess the quality of life (QOL). Physical fitness is an important determinant of QOL, and because cardiac function can influence exercise performance, it is the purpose of the present study to assess these factors. METHODS: Children in stable follow-up for more than 6 months post-LT were invited to participate in a case control study. Patients underwent cardiopulmonary exercise testing and echocardiography to assess systolic and diastolic function, and left ventricular wall dimensions. Health-related QOL was evaluated using child- and adolescent-reported PedsQL questionnaire. RESULTS: Twenty-eight of 31 included patients performed a maximal exercise test (15 boys, 11.6 ± 2.9 years, weight, 40.9 ± 13.1 kg; length, 148.6 ± 17.3 cm; body mass index, 17.6 ± 2.3). Liver transplantation patients had lower maximal oxygen consumption (VO2max/kg) (37.5 ± 9.3 mL/kg per minute vs 44.1 ± 8.8 mL/kg per minute), shorter exercise duration (9.3 ± 2.8 minutes vs 13.3 ± 3 minutes) and lower load (71 ± 14 vs 85 ± 20%). They reached the ventilatory anaerobic threshold earlier (81.4 ± 9.5 vs 88.3 ± 11.9%). Echocardiography demonstrated increased interventricular septal wall thickness (interventricular septum in diastole Z value, +0.45 ± 0.49, P < 0.001) and more diastolic dysfunction (lower E', Z value, -0.7 ± 1.02, P = 0.002, higher E/E' Z value, 0.64 ± 1.05. P = 0.005) but no relations with cardiopulmonary exercise testing. Health-related QOL showed lower overall, emotional, psychosocial, and school functioning scores. Children on antihypertensive medication had impaired physical functioning compared with other LT patients. CONCLUSIONS: Lower physical fitness level, more deconditioning and lower health-related QOL in children after LT emphasize the importance of exercise stimulation and fitness programs. Patients on antihypertensive medication seem to be the most vulnerable group suffering from decreased physical fitness.

Pulmonary function in children after surgical and percutaneous closure of atrial septal defect.

This study aimed to study differences in lung function after surgical and percutaneous atrial septal defect (ASD) closure. Several studies have demonstrated abnormalities of pulmonary function in adults and children with ASD. These abnormalities persist even a few years after correction. This study compared pulmonary function between patients who underwent ASD closure by surgery and those who had closure by device. This is the ideal pediatric population for studying changes in lung function caused by cardiopulmonary bypass or sternotomy. The 46 patients in this study were treated by percutaneous closure (group 1) or surgical closure (group 2) of ASD and then scheduled for pulmonary function testing an average of 5.8 years after ASD closure. The mean values of functional residual capacity, total lung capacity, and residual volume did not differ between the two groups. The surgical group showed a significant decrease in expiratory reserve volume (p < 0.04) and forced vital capacity (p < 0.03). Expiratory flow at 25, 50, and 75% of forced vital capacity did not differ between the two groups but was on the lower limit of normal in both groups. Percutaneous closure of ASD can minimize the side effects of surgical closure on lung function. Longitudinal lung function follow-up assessment after cardiac surgery is warranted to detect and measure restrictive abnormalities in this type of congenital heart disease and others.