Echocardiographic Parameters Associated With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Children's exposure to chemotherapeutic agents causes several long-term adverse effects but physical activity has been evidenced to be an effective strategy to improve cardiac function. This cross-sectional study aimed to explore the association between physical activity levels, cardiorespiratory fitness, and cardiac parameters measured by echocardiography. METHODS: Participants were 216n childhood acute lymphoblastic leukemia survivors who underwent a maximal cardiopulmonary exercise test and self-reported their daily minutes of moderate to vigorous physical activity. They underwent a complete transthoracic echocardiographic assessment. Systolic and diastolic function analysis and strain images analysis were performed. The associations were studied through the preventive fraction (examined with univariate crude and adjusted logistic regression models) of regular physical activity (≥150 min·wk-1) and adequate cardiorespiratory fitness levels (above the median ≥ 32.0 mL·kg-1·min-1) on cardiac parameters. RESULTS: Crude analysis shows that regular physical activity was associated with a significant preventive fraction in mitral E/A ratio (56%; P = .013), while adjusted analyses highlighted a nonsignificant reduction of 74% to 37% in the prevalence of cardiac parameters associated with physical activity. Similar associations of adequate cardiorespiratory fitness on cardiac parameters were observed. Adjusted analyses revealed a nonsignificant reduction of 7% to 86% in the prevalence of cardiac parameters associated with cardiorespiratory fitness. CONCLUSION: This study reports that regular physical activity and adequate cardiorespiratory fitness were associated with a higher preventive fraction. Thus, engaging in physical activity prevents childhood acute lymphoblastic leukemia survivors' cardiac dysfunctions. These findings are novel and clinically relevant in pediatric cardiooncology and provide additional evidence to strengthen the benefits of exercise as long-term care in childhood cancer survivors.

Cardiopulmonary response to exercise in adults born very preterm.

This study aims to compare cardiopulmonary response to aerobic exercise between young adults born very preterm, including a subgroup with bronchopulmonary dysplasia (BPD), and term controls.Seventy-one adults (18-29 years) born <30 weeks' gestational age (24 with BPD) and 73 term controls were recruited. Assessment included cardiopulmonary exercise testing with impedance cardiography. We compared group differences in peak O2 consumption (peak VO2) and in ventilatory and cardiovascular responses to exercise using linear regression analyses.Preterm participants had reduced peak VO2 (mean difference -2.7; 95% CI -5.3, -0.1 mL·kg-1 lean body mass·min-1) versus controls. Those with BPD achieved lower peak work-rate compared to term controls (-21; 95% CI -38, -5 watts). There was no difference across groups in breathing reserve, ventilatory efficiency, peak heart rate and cardiac output. VO2 to work-rate relationship (ΔVO2/ΔWR) was reduced in preterm versus term. Peak systolic blood pressure and circulatory power (systolic blood pressure*VO2) were also lower in BPD versus term controls. In the preterm group, longer NICU stay and lower peak cardiac output were associated with lower peak VO2Results suggest limitations with peripheral O2 uptake in the muscle with reduced ΔVO2/ΔWR and peak circulatory power, but normal cardiac output. Investigations into skeletal muscle perfusion and O2 use during exercise are warranted to better understand mechanisms of exercise limitation.

Relationship between cardiac mechanical properties and cardiac magnetic resonance imaging at rest in childhood acute lymphoblastic leukemia survivors.

The characterization of cardiac mechanical properties may contribute to better understanding of doxorubicin-induced cardiotoxicity. Our study aims to investigate the relationship between cardiac mechanical properties, T1 and T2 relaxation times and partition coefficient. Fifty childhood acute lymphoblastic leukemia survivors underwent a cardiac magnetic resonance (CMR) at rest on a 3T MRI system and included a standard ECG-gated 3(3)3(3)5 MOLLI sequence for T1 mapping and an ECG-gated T2-prepared TrueFISP sequence for T2 mapping. Partition coefficient, ejection fraction, end-diastolic volume (EDV) and end-systolic volume (ESV) were calculated. CircAdapt model was used to study cardiac mechanical performance (left ventricle stiffness (LVS), contractility (LVC) and pressure (Pmin and Pmax), cardiac work efficiency (CWE) and ventricular arterial coupling). In the whole cohort, our results showed that LVC (R2 = 69.2%, r = 0.83), Pmin (R2 = 62.9%, r = 0.79) and Pmax can be predicted by significant CMR parameters, while T1 (R2 = 23.2%, r = 0.48) and partition coefficient (R2 = 13.8%, r = 0.37) can be predicted by significant cardiac mechanical properties. In SR group LVS (R2 = 94.8%, r = 0.97), LVC (R2 = 93.7%, r = 0.96) and Pmin (R2 = 90.6%, r = 0.95) can be predicted by significant cardiac mechanical properties, while in HR + DEX group CWE (R2 = 49.8%, r = 0.70) can be predicted by significant cardiac mechanical properties. Partition coefficient (R2 = 72.6%, r = 0.85) can be predicted by significant CMR parameters in SR group. Early characterization of cardiac mechanical properties from CMR parameters has the potential to early detect doxorubicin-induced cardiotoxicity.

Cardiac Mechanical Performance Assessment at Different Levels of Exercise in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: There is a shortage of relevant studies interested in cardiac mechanical performance. Thus, it is clinically relevant to study the impact of cancer treatments on survivors' cardiac mechanical performance to improve our knowledge. The first objective of this study is to assess survivors' cardiac mechanical performance during a cardiopulmonary exercise test (CPET) using both ventricular-arterial coupling (VAC) and cardiac work efficiency (CWE) from cardiac magnetic resonance (CMR) acquisitions. The second objective is to assess the impact of doxorubicin and dexrazoxane (DEX) treatments. METHODS: A total of 63 childhood acute lymphoblastic leukemia survivors underwent a CMR at rest on a 3T magnetic resonance imaging system, followed by a CPET on ergocycle. The CircAdapt model was used to study cardiac mechanical performance. At different levels of exercise, arterial elastance, end-systolic elastance, VAC, and CWE were estimated. RESULTS: We observed significant differences between the different levels of exercise for both VAC ( P <0.0001) and CWE parameters ( P =0.001). No significant differences were reported between prognostic risk groups at rest and during the CPET. Nevertheless, we observed that survivors in the SR group had a VAC value slightly lower than heart rate (HR)+DEX and HR groups throughout the CPET. Moreover, survivors in the SR group had a CWE parameter slightly higher than HR+DEX and HR groups throughout the CPET. CONCLUSIONS: This study reveals that the combination of CPET, CMR acquisitions and CircAdapt model was sensitive enough to observe slight changes in the assessment of VAC and CWE parameters. Our study contributes to improving survivors' follow-up and detection of cardiac problems induced by doxorubicin-related cardiotoxicity.

Modelling cardiac mechanics in doxorubicin-induced cardiotoxicity following childhood acute lymphoblastic leukemia using a combination of cardiac magnetic resonance imaging, cardiopulmonary exercise testing and the CircAdapt model.

Children with acute lymphoblastic leukemia (ALL) are treated with doxorubicin-based chemotherapy that can lead to cardiotoxicity which is a well-known cause of mortality. This study aims to characterize myocardial subtle changes induced by doxorubicin-related cardiotoxicity. We used the combination of cardiac magnetic resonance (CMR) imaging, cardiopulmonary exercise testing and the CircAdapt model to explore hemodynamics and intraventricular mechanisms at rest and during exercise in 53 childhood ALL survivors. A sensitivity analysis of the CircAdapt model identified the most influencing parameters on the left ventricle volume. ANOVA were performed to explore significant differences between left ventricle stiffness, contractility, and arteriovenous pressure drop, as well as survivors' prognostic risk groups. No significant differences were observed between prognostic risk groups. The left ventricle stiffness and left ventricle contractility were non-significantly higher in survivors receiving cardioprotective agents (94.3 %), compared to those at standard and high prognostic risk (77 % and 86 %, respectively). In both left ventricle stiffness and left ventricle contractility, we observed that survivors receiving cardioprotective agents were close to the nominal value of CircAdapt (healthy reference group value is 100 %). This study allowed to improve our knowledge of potential subtle myocardial changes induced by doxorubicin-related cardiotoxicity in childhood ALL survivors. This study confirms that survivors exposed to a high cumulative dose of doxorubicin during treatments are at potential risk of myocardial changes many years after the end of their cancer, while cardio-protective agents may prevent changes in cardiac mechanical properties.

Cardiorespiratory Fitness and Cardiac Magnetic Resonance Imaging in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Childhood acute lymphoblastic leukemia survivors' anthracycline-induced cardiotoxicity could be prevented with good cardiorespiratory fitness levels and regular physical activity. This cross-sectional study aimed to assess the association between cardiorespiratory fitness and physical activity with cardiac magnetic resonance parameters. METHODS: A total of 96 childhood acute lymphoblastic leukemia survivors underwent a maximal cardiopulmonary exercise test and answered physical activity questionnaires. We calculated the odds ratio of the preventive fraction of regular physical activity (≥150 min/wk) and adequate cardiorespiratory fitness levels (above the median ≥31.4 mL·kg-1·min-1) on cardiac magnetic resonance parameters (left ventricular [LV] and right ventricular [RV] morphological and functional parameters). RESULTS: An adequate cardiorespiratory fitness was associated with a significant preventive fraction for LV (up to 84% for LV end-diastolic volume) and RV volumes (up to 88% for RV end-systolic volume). The adjusted analyses highlighted a preventive fraction of 36% to 91% between an adequate cardiorespiratory fitness and LV and RV parameters, late gadolinium enhancement fibrosis, and cardiac magnetic resonance relaxation times. No associations were reported with regular physical activity. CONCLUSIONS: This study provides additional evidence regarding the benefits of an adequate cardiorespiratory fitness level for childhood cancer survivors' cardiac health.

Estimation of anisotropic properties of CMR patient-specific left ventricle using the virtual field method.

Left ventricle (LV) myocardial dysfunction has been recently investigated using the estimation of isotropic myocardial stiffness from magnetic resonance imaging (MRI). However, Myocardium is known to have a 3D complex geometry with anisotropic stiffness. The assessment of the anisotropy properties characterizes structural changes in myocardium as a consequence of heart failure (HF). From image data, the virtual field method (VFM) can determine material stiffness in a non-invasive manner. In the present work, the objective is to compare two inverse identification methods, given the isotropic and anisotropic models in the characterization of properties of myocardium in acute lymphoblastic leukemia (ALL) survivors using VFM and MRI. Two types of VFM approach are presented. Using the first, the virtual displacements (VFs) allow whole-field LV to be imposed into VFM formulation and caused to directly estimate two independent parameters from isotropic constitutive relation. With the second, anisotropic parameters are estimated using piece-wise (Finite element-based) VFM. The resulting values showed significant differences between the subjects in comparative study of leukemia survivors, and variance in estimated parameters by two different VFM approach. This approach would be an efficient tool to characterize early cardiac dysfunction. This work elucidates the benefits and shortcomings of using VFM to determine anisotropic parameters of LV myocardium in linear elastic and of using the FEM application to generate meshes of patient-specific LVs from MRI images.

Dexrazoxane Treatments Limits Subclinical Cardiac Dysfunction in Childhood Acute Lymphoblastic Leukemia Survivors Exposed to Doxorubicin Treatments.

INTRODUCTION: Doxorubicin leads to dose dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. We investigated survivors' heart health using echocardiography and evaluated doxorubicin and dexrazoxane treatments on cardiac function. METHODS: A total of 196 childhood ALL survivors were stratified (standard risk [SR], high risk with and without dexrazoxane (HR+DEX and HR). We performed a complete transthoracic echocardiographic assessment with M-mode echocardiography, Doppler, and Tissue Doppler. We used 2-dimensional and 3-dimensional echocardiography to measure the left ventricular ejection fraction, whereas myocardial strain imaging was used to obtain global strain indices. RESULTS: Although most cardiac and arterial dimension parameters were not different between groups, a difference was observed in posterior intima of the right carotid ( P =0.017). Diastolic functions analyses reported that LV shortening fraction and left and right ventricular lateral S' wave amplitudes were lower in HR than in SR and HR+DEX groups ( P =0.028, P =0.048, and P =0.005, respectively). The LV lateral E' in diastolic function was lower in the HR than in SR and HR+DEX groups ( P =0.036). The LV end-systolic wall stress was higher in HR than in SR and HR+DEX groups ( P =0.009). A decrease contractility was observed, while the effect was not group specific. Strain rate was not different between groups, as opposed to tissue Doppler measurements. CONCLUSIONS: This study showed that dexrazoxane treatments could limit subclinical cardiac dysfunction in childhood ALL survivors, whereas survivors in HR group who did not receive dexrazoxane had potential subclinical cardiac damage observable in heart failure patients. Echocardiographic screening for survivors must be part of the follow-up routine in cardio-oncology.

The effect of different aero handlebar positions on aerodynamic and gas exchange variables.

Adopting the time trial position (TTP) represents a notable improvement for cycling aerodynamic performance. Aero handlebars are designed to enable the cyclist to adopt a more aerodynamic TTP. However, it is unclear to what realistic extent the aero handlebar configuration affects the aerodynamics and physiological functioning. Thus this study aimed to investigate the effect of aero handlebar alterations on gas exchange parameters and aerodynamics of TTP. Seven male competitive cyclists and triathletes performed submaximal tests on a cycle ergometer at six different TTPs. Oxygen uptake, respiratory exchange ratio, minute ventilation and tidal volume were collected. Using the computational fluid dynamics (CFD) method, the detailed airflow patterns around the cyclist were investigated. The results were analyzed in terms of drag area, velocity and pressure distributions around the cyclist, surface pressure coefficient and wall shear stress magnitude. It was revealed that varying the aero handlebar position significantly influences aerodynamic performance, while maximal values of all the gas exchange variables remained unchanged. Compared to the cyclist's preferred TTP, the frontal area, drag coefficient and drag area were reduced by 4.1%, 4.6% and 8.5%, respectively, when lowering the handlebar position by 5 cm, which overcomes the metabolic costs.

Detection of doxorubicin-induced cardiotoxicity using myocardial T1 and T2 relaxation times in childhood acute lymphoblastic leukemia survivors.

Doxorubicin leads to dose-dependent cardiotoxicity in childhood acute lymphoblastic leukemia (ALL) survivors. The first aim was to propose a contour-based estimation of T1 and T2 relaxation times based on the myocardial area, while our second aim was to evaluate native T1, post-gadolinium T1 and T2 relaxation time sensitivity to detect myocardial changes. A total of 84 childhood ALL survivors were stratified in regard to their prognostic risk groups: standard risk (SR), n = 20), high-risk with and without dexrazoxane (HR + DEX, n = 39 and HR, n = 25). Survivors' mean age was of 22.0 ± 6.9 years, with a mean age at cancer diagnosis of 8.0 ± 5.2 years. CMR acquisitions were performed on a 3 T MRI system and included an ECG-gated 3(3)3(3)5 MOLLI sequence for T1 mapping and an ECG-gated T2-prepared TrueFISP sequence for T2 mapping. Myocardial contours were semi-automatically segmented using an interactive implementation of cubic Bezier curves. We found excellent repeatability between operators for native T1 (ICC = 0.91), and good repeatability between operators for post-gadolinium T1 (ICC = 0.84) and T2 (ICC = 0.79). Bland and Altman tests demonstrated a strong agreement between our contour-based method and images analyzed using the CVI42 software on the measure of native T1, post-gadolinium T1, and T2. No significant differences between survivors' prognostic risk groups in native T1 were reported, while we observed significant differences between survivors' prognostic risk groups in post-gadolinium T1 and T2. Significant differences were observed between male and female survivors. Differences between groups were also observed in partition coefficients, but no significant differences were observed between male and female survivors. The use of CMR parameters with native T1, post-gadolinium T1, and T2 allowed to show that survivors at a high-risk prognostic were more exposed to doxorubicin-related cardiotoxicity than those who were at a standard risk prognostic or who received dexrazoxane treatments.

Doxorubicin treatments induce significant changes on the cardiac autonomic nervous system in childhood acute lymphoblastic leukemia long-term survivors.

AIMS: Acute lymphoblastic leukemia (ALL) is one of the leading malignancies in children worldwide. The cardiotoxicity of anti-cancer treatments leads to a dysfunction of the cardiac autonomic nervous system. Protection strategies, with dexrazoxane treatments, were used to counter these adverse effects. The aim of this study was to investigate the effects of the treatments on the cardiac autonomic nervous system. METHODS AND RESULTS: A total of 203 cALL survivors were included in our analyses and were classified into 3 categories based on the prognostic risk group: standard risk, high risk with and without dexrazoxane. A 24-h Holter monitoring was performed to study the cardiac autonomic nervous system. The frequency domain heart rate variability (HRV) was used to validate the cardiac autonomic nervous system modifications. Other analyses were performed using linear HRV indexes in the time domain and non-linear indexes. A frequency domain HRV parameters analysis revealed significant differences on an overall time-period of 24 h. A repeated measures ANOVA indicated a group-effect for the low frequency (p = 0.029), high frequency (p = 0.03) and LF/HF ratio (p = 0.029). Significant differences in the time domain and in the non-linear power spectral density HRV parameters were also observed. CONCLUSION: Anti-cancer treatments induced significant changes in the cardiac autonomic nervous system. The HRV was sensitive enough to detect cardiac autonomic nervous system alterations depending on the cALL risk category. Protection strategies (i.e., dexrazoxane treatments), which were used to counter the adverse effects of doxorubicin, could prevent changes observed in the cardiac autonomic nervous system.

To distinguish flexible and rigid lumbar curve from MRI texture analysis in adolescent idiopathic scoliosis: A feasibility study.

BACKGROUND: Imaging in side bending, supine, traction, fulcrum, and push prone are examples of methods used to evaluate the curve reduction of scoliotic spine. However, being able to determine spine curve flexibility from MRI would eliminate the need of additional X-ray radiation related to radiograph acquisition in side-bending. PURPOSE/HYPOTHESIS: To find specific texture features of lumbar postural muscles on MRI that can distinguish flexible from rigid lumbar scoliotic curves. We hypothesized that the changes occurring in postural muscles with scoliosis can be seen with MRI. STUDY TYPE: Retrospective study case control. POPULATION: With Institutional Review Board approval and informed consent, 15 adolescents with idiopathic scoliosis and scheduled for surgery were involved. FIELD STRENGTH/SEQUENCE: T1 -weighted MR images were performed on a 1.5T system using a spin echo sequence in the axial direction. ASSESSMENT: The spinal erector, quadratus lumborum and psoas major muscles were analyzed using textural features. STATISTICAL TESTS: Principal component analysis (PCA) and agglomerative hierarchical clustering (AHC) were used to classify the lumbar postural muscles and calculate performance metrics. The lumbar flexibility index, measured from suspension tests, was used as ground truth measurement. RESULTS: The five discriminant features (out of 34 tested features) obtained from PCA were able to keep over 90% of the variability of the dataset. The right and left spinal erector and the left psoas major had the highest performance metrics to classify the spinal curve flexibility, with an accuracy over 0.80, a sensitivity over 0.82, a specificity over 0.68, and a Matthews correlation coefficient over 0.57. DATA CONCLUSION: This study analyzed MRI using texture information of muscle to distinguish flexible from rigid scoliotic curves. Some postural muscle such as the spinal erector and the psoas major are more likely to reflect the curve flexibility of a scoliotic participant. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2017.

Imaging of early modification in cardiomyopathy: the doxorubicin-induced model.

Doxorubicin chemotherapy is effective and widely used to treat acute lymphoblastic leukemia. However, its effectiveness is hampered by a wide spectrum of dose-dependent cardiotoxicity including both morphological and functional changes, affecting primarily the myocardium. Non-invasive imaging techniques are used for the diagnosis and monitoring of these cardiotoxic effects. The purpose of this review is to summarize and compare the most common imaging techniques used in early detection and therapeutic monitoring of doxorubicin-induced cardiotoxicity and the suggested mechanisms of such side effects. Imaging techniques using echocardiography including conventional 2D and 3D echocardiography along with MRI sequences including Tagging, Cine, and quantitative MRI in detecting early myocardial damage are also reviewed. As there is a multitude of reported indices and imaging methods to assess particular functional alterations, we limit this review to the most relevant techniques based on their clinical application and their potential to early detection of doxorubicin-induced cardiotoxic effects.