Non-invasive Monitoring of Cardiac Hemodynamic Parameters in Doxorubicin-treated Patients: Comparison with Echocardiography

Abstract

Cardiotoxicity represents the major factor that limits the use of anthracyclines in long-term cancer chemotherapy, therefore, the early detection of cardiac dysfunction is very important. Currently, the left ventricular ejection fraction is routinely used to screen cardiotoxicity. The most common methods in use are represented by 2-dimensional (2D) echocardiography and radionuclide angiography. The aim of the present investigation was to compare the findings obtained in patients subjected to doxorubicin (DXR) chemotherapy, by 2D echocardiography with hemodynamic parameters, resulting from a new non-invasive method based on an inert gas rebreathing technique. The study was conducted in 35 adult female patients (mean age 48 years, range 30 - 67) submitted to chemotherapy for metastatic breast cancer with DXR and paclitaxel. DXR was administered at a dose of 60 mg/m² and paclitaxel at a dose of 200 mg/m² every 3 weeks for a maximum of 8 cycles. Heart function evaluation was performed before initiating chemotherapy, after 3 cycles, 1 month after the completion of chemotherapy and when clinically requested. The mean cumulative dose of DXR, in patients who had received at least 4 or more cycles, was 320 mg/m² of body surface area with a range of 240 to 480 mg/m². The data obtained with 2D echocardiography (left ventricular end diastolic and systolic dimensions and ejection fraction) were compared with hemodynamic parameters obtained by the inert gas rebreathing technique (cardiac output, stroke volume, cardiac index and stroke index). Hemodynamic monitoring showed a progressive decrease of all parameters during DXR treatment, which became statistically significant at the end of the treatment. A significant reduction of ejection fraction due to an increase in the end systolic dimension of the left ventricle, without significant modification of the end diastolic dimensions, was observed. A good correlation was found between data obtained with the echocardiographic method and those obtained by the inert gas rebreathing technique. Two patients showed symptoms of congestive heart failure, the deterioration of cardiac function was simultaneously detected by both methods. These data confirm that cardiac function deterioration is detectable at a cumulative dose lower than 550 mg/m² and that the inert gas rebreathing method for the determination of hemodynamic parameters could represent an alternative tool, in addition to conventional echocardiographic examination, in the evaluation of anthracycline-induced cardiotoxicity.