Study Population
In this cohort study, 60 patients referred to Shahid Faghihi hospital who were supposed to be treated with anthracycline agents were enrolled. These patients were in the range of 30-70 years old and without any cardiovascular problems. The patients with a history of myocardial infarction, COPD, Valvular heart disease, congenital heart disease, previous CABG, pace-maker usage, and LV dysfunction were excluded from the study. All patients gave informed written consent. This study was approved by the Ethics Committee of Shiraz University of Medical Sciences by approval number of IR.SUMS.MED.REC.1399.013 and is based on the declaration of Helsinki.
Study design and protocol
For all the patients, baseline echocardiography was performed before the initiation of the chemotherapeutic regimen and repeated 6 months later when the chemotherapy was stopped. Blood samples were obtained after completing the treatment course for determination of the troponin level. The function of both LV and RV was checked to find the correlation of RV changes with incidence of anthracycline cardiac toxicity (AT-CMP). AT-CMP was defined based on the definition by American society of echocardiography as either more than 10 percent drop in LVEF, 15% drop in GLS, LVEF drop below 50%, GLS drop below -19%, or pathological rise in the troponin level.[11]
Echocardiographic studies
For all patients, a baseline echocardiography study was done before the initiation of chemotherapy and a follow up after 6 months when chemotherapy was finished. Two-dimensional transthoracic echocardiography (2D-TTE) was used to evaluate the patient’s cardiac structure, LVEF, and Global Longitudinal Strain (GLS). All patients were imaged in the left lateral decubitus position, using the general electric E9 conventional echocardiography machine (GE, USA). The transducer was placed in the left midclavicular line in the 4th to 5th intercostal spaces, where the point of maximal impulses of the heart (PMI) was detected. A specified reader analyzed all the echocardiograms. LVEF was calculated by the 2D-TTE probe from the apical 4-chamber view, using an automated 2D protocol method.
Speckle-tracking echocardiography was performed using the same machine; the displacement of the myocardial speckles in each spot was analyzed and tracked frame to frame. The longitudinal strain was assessed using automated functional imaging (AFI). The global longitudinal peak strain was automatically calculated as an averaged value of the peak longitudinal strain in all 3-image planes (apical 2- and 4-chamber and long-axis views) (Figure 1).
The right ventricular end-diastolic and end-systolic areas were measured from the apical four-chamber view to calculate the right ventricular fractional area change (RVFAC) using following formula:
RVFAC (%) = (RV end-diastolic area − RV end-systolic area) / RV end-diastolic area × 100 (Figure 1)
RV free wall longitudinal strain (RV LSFW) was assessed by averaging basal, mid, and apical segments of RV lateral wall using Automated Functional Imaging (AFI). Global longitudinal strain was also measured automatically with the same method as the mean of basal, mid, and apical segments of the RV lateral wall and septum in four chamber views.
TAPSE was measured trough M-Mode using the distance between the end-diastolic to end- systolic point in apical four-chamber view by placing the cursor along the tricuspid lateral annulus. The tricuspid annular systolic velocity was measured using tissue Doppler. In this method, the sample volume placed at the tricuspid lateral annulus and Peak systolic (Sa) was calculated. The echocardiography was done by an authorized cardiologist who was blinded to all other parts of the study. The TTE was repeated six months later immediately after completion of chemotherapy course.
Serum Biomarkers Measurement
All the patients underwent measurement of highly sensitive troponin I measurement at baseline before staring chemotherapy and after 6 months using enzyme-linked immunosorbent assay (ELISA) kits (bioassay technology laboratory, China).
Statistical analysis
The analysis of the parametric data was shown by the mean and standard deviation. Qualitative and classified data were presented based on the number and percentage. Data were analyzed using SPSS (v.22. IBM Inc. IL). The normality Kolmogorov-Smirnov test was carried out to estimate whether continuous variables were normally distributed. Qualitative and classified data were presented based on the number and percentage and the univariate analysis on quantitative and qualitative data using Independent and paired samples’ t-test and Chi-square tests. The P-value less than 0.05 was considered significant.