Simulation de l'hémodynamique ventriculaire gauche pour la caractérisation de la cardiotoxicité induite par la doxorubicine

Objective: Doxorubicin-based chemotherapy has largely improved the survival rates in patients suffering from childhood acute lymphoblastic leukemia (cALL). However, it has been associated with a significant cardiotoxicity and induced cardiomyopathy both during treatment and years after remission. What’s more, the higher the cumulative dose of recieved doxorubicin is, the higher the risk of developping a cardiomyopathy years after the end of the treatment will be. The resulting damage on cardiac muscles has been studied and described multiple times, using medical imaging et modelling techniques. Yet, early diagnosis of these cardiotoxic effects remain a challenge, in order to identify patients at risk, but also to characterise heart failure. This study aims to characterise blood flow inside the left ventricle, which is yet to be studied in these patients, using patient-specific modelling based on medical imaging. To acheive this goal, a pre-existing model (CircAdapt) is used, as well as as a new method to model patient-specific blood flow inside the left ventricle based on cardiac magnetic resonance (CMR) imaging. Scientific approach and methods: In this study, analysis of the left ventricular hemodynamics in cALL survivors is presented. A cohort of patients from the PETALE project is divided into three groups based on the cumulative dose of doxorubicin received, namely: HR (High Risk, who received more than 200mg/m2), SR (Standard Risk, who received less than 200mg/m2) and HRdex HR (High Risk, who received more than 200mg/m2, along with a cardioprotective agent, dexrazoxan). The left ventricular hemodynamics is analysed following two different methods. The first method is based on the personalisation of the CircAdapt model, a lumped model of the heart and circulation, based on adaptable inputs. To personalise the model, inputs of interest were identified using a sensitivity analysis based on the Morris method. The most impacting inputs were selected, and among these variables, the ones that were monitored were personalised, and the ones that were not were reverse optimised in order to correlate measured outputs and simulated outputs. E/A ratio measured by Doppler echocardiography and arterial pressure measured by ECG gated cuff were used for reverse optimisation. The optimised and patient-specific model is the used to simulate exercise, by using heart rate, cardiac output, and mean arterial pressure monitored during cardiopulmonary exercise test-ing (CPET). Mean speed at the aortic and mitral valve are then extracted through time and compared between different groups of patients (HR, SR, HRdex).