Prediction of Delayed Toxic Cardiomyopathy in Children

Study Overview
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Brief Summary
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Longitudinal analysis of myocardial function using Speckle Tracking Echocardiography STE analysis and prediction of delayed toxic induced cardiomyopathy in young patients who received anthracycline therapy in childhood.

Detailed Description
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Anthracycline therapy may have short-, medium- or long-term cardiac toxicity that impacts patient's life. The main recognized risk factors for delayed cardiotoxicity are cumulative anthracycline dose, female gender, association with mediastinal radiotherapy and young age at administration. Prediction of delayed cardiotoxicity in children population is still challenging. The Speckle Tracking Echocardiography (STE) method, an innovative echocardiographic technique, analyses the myocardial displacement of natural acoustic markers via a software. The objective of the study is to analyze, in young patients who received anthracycline therapy in childhood, 5-years after their inclusion in the Speckle Anthra study and first STE results, the evolution of myocardial function using STE method.

Official Title
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Longitudinal Analysis of Myocardial Function by Speckle Tracking Echocardiography and Prediction of Delayed Toxic Cardiomyopathy Associated With Anthracycline Therapy in Children

Conditions
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Cardiotoxicity, Childhood Cancer

Intervention / Treatment
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* Diagnostic Test: cardiac ultrasound with speckle tracking analysis


Participation Criteria
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Eligibility Criteria
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ANTHRA GROUP Inclusion Criteria: Patients who were treated with anthracyclines for malignant disease between the ages of 0 and 18 Patient aged 11 to 27 years Included in the SpeckleAnthra Study (NCT02893787) Discontinued chemotherapy for more than 6 years Patient in remission of malignant disease Enrolled in a social security plan Written informed consent from at least one legal representative for the minor patient/ Written informed consent for patients of legal age Exclusion Criteria: Onset of active malignancy or recurrence of malignancy after the Speckle Anthra study that required resumption of chemotherapy or mediastinal radiotherapy. Chronic cardiac, pulmonary or muscular pathology of etiology other than secondary to anthracycline therapy For adult patients: subject under guardianship or curators CONTROL GROUP Inclusion Criteria: Control patient included in the Speckle Control study (NCT02056925) Had a cardiological consultation with echocardiography performed for a banal reason (heart murmur test, cardiological symptoms) and whose result was normal No chronic disease or long-term drug treatment Exclusion Criteria: Refusal to participate in the study by the patient and/or parents or legal guardian after receipt of the study's information and non-objection note.

Ages Eligible for Study
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Minimum Age: 11 Years
Maximum Age: 27 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anthra2<br>Patient will have an echocardiography with speckle tracking analysis 5 years after the end of their participation to SpeckleAnthra study (NCT02893787) | Diagnostic Test: cardiac ultrasound with speckle tracking analysis<br>* Experimental group: cardiac ultrasound with speckle tracking analysis done during a regular cardiac visit planned after receiving cardiotoxic chemotherapy in childhood. Control group: cardiac ultrasound with speckle tracking analysis done during a cardiac visit for minor symptoms (murmur, physical aptitude). Advocated Tomtec software will be used to make post-processing speckle tracking analysis based on 2D ultrasound cineloop acquired during a standard echocardiography.<br>|
| Active Comparator: Control<br>Cardiac ultrasound analysis with speckle tracking of age- and sex-matched healthy patients in the Anthra2 group | Diagnostic Test: cardiac ultrasound with speckle tracking analysis<br>* Experimental group: cardiac ultrasound with speckle tracking analysis done during a regular cardiac visit planned after receiving cardiotoxic chemotherapy in childhood. Control group: cardiac ultrasound with speckle tracking analysis done during a cardiac visit for minor symptoms (murmur, physical aptitude). Advocated Tomtec software will be used to make post-processing speckle tracking analysis based on 2D ultrasound cineloop acquired during a standard echocardiography.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricle Global Longitudinal 2D strain (LVGLS) expressed in percentage and obtained from cardiac ultrasound cineloop of 2D 4,3 and 2 apical views analyzed by the Tomtec STE Software. | To compare the evolution at 5 years (Anthra2 study timeframe) of LVGLS obtained by STE analysis on patients treated with anthracyclines in childhood and previously included in first Speckle Anthra study, with the normal evolution of this parameter with age in healthy matched volunteers. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left Ventricle Ejection fraction (LVEF) by Simpson method (%) | Compare the standard ultrasound parameter LVEF and the LVGLS obtained in Speckle Anthra 2 on patients treated with anthracyclines in childhood and in the group of healthy volunteers. | The day of inclusion | 
| Left ventricular myocardial dysfunction defined by LVEF < 55% | Correlation between the left ventricular myocardial dysfunction is defined by FeVG < 55% and the left global longitudinal 2D strain expressed in percentage and measured during the previous SpeckleAnthra study | 5 years | 
| Death secondary to toxic cardiomyopathy | Correlation between the rate of patients died with a toxic cardiomyopathy and the left global longitudinal 2D strain expressed in percentage and measured during the previous SpeckleAnthra study | 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Echocardiography, Ventricular function, Stroke Volume