الفهرس 
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Abstract
SUMMARY
B
reast cancer is the most commonly diagnosed cancer in Women worldwide, and it is the fifth leading cause of cancer death. Anthracyclines and HER-2 inhibitor (Trastuzumab) are the mainstay of chemotherapy for breast cancer and despite their clear therapeutic effects on prolonging survival, they led to large spectrum of cardiotoxicity manifestations ranging from asymptomatic heart failure to clinically overt picture of heart failure.
Anthracyclines work by inhibiting DNA replication and transcription. Its cardiotoxic effect proved to be in a dose dependent pattern with incidence of heart failure 5% with average cumulative dose 400 mg/m2, but it reaches 48% with average cumulative dose 700 mg/m2. Conversely Trastuzumab induced cardiotoxicity, firstly detected in 2001 in phase III clinical trial, is not dose dependent and thought to be due to altering the expression of genes responsible for DNA repair and mitochondrial function leading to impaired systolic performance.
Traditionally follow-up of patients receiving chemotherapy was done by clinical surveillance of heart failure symptoms together with LV EF measurement. Despite the prognostic importance of EF measurement, it isn`t sensitive enough to detect early changes in myocardial function. This is due to method problems like inadequate LV apex visualization, the need for geometrical assumption for calculations and the variability of measurements in addition to that a detectable change in EF occurs after a considerable loss of the myocardium.
Because of the pre-mentioned causes, LVEF reduction is often a late phenomenon with failure to recover in 58% of the cases despite intervention with mortality from heart failure due to anthracycline induced cardiotoxicity as high as 60% in 2 years. That`s why there is a growing interest in identifying the earliest markers of myocardial change which can predict subsequent DROP in EF. LV strain parameters measurement was used for early assessment of myocardial changes and LV GLS was recommended by ASE/EACVI expert consensus to be measured with follow-up of it during the chemotherapy treatment.
There is paucity of literature about the effect of chemotherapy on RV function and strain parameters and whether these changes are more common than LV changes and if RV changes are earlier than LV. Also it`s questionable if changes in GLS values for the RV could predict LV EF DROP or not. In this study we aimed at studying changes in LV & RV mechanics during the chemotherapy treatment and detecting the strongest predictor of subsequent cardiotoxicity. Cardiotoxicity was defined decrease in EF > 10% from baseline value to EF < 55% in asymptomatic patients or > 5% in symptomatic patients “as defined by the cardiac review and evaluation committee (CREC)”.
The current study included asymptomatic female patients diagnosed with non-metastatic breast cancer who were scheduled to receive chemotherapy. Exclusion criteria included history of previous chemotherapy or radiotherapy, reduced LV EF < 50%, a history of coronary artery disease, patients with severe valvular disease or primary cardiomyopathy, history of medical diseases affecting right ventricular function (e.g corpulmonale,..) and patients with Atrial Fibrillation or with permanent pacemakers. Traditional cardiovascular risk factors as hypertension, diabetes, chronic kidney disease, smoking, hypothyroidism and obesity (BMI) were recorded in our study population.
A comprehensive resting ECG gated transthoracic echocardiography was done for all patients and measurements were done according to American Society of Echocardiography recommendations. Measurement of different LV strain values (GLS, GCS, GRS) and RV (GLS, FWLS) was done for all patients. All these measurements were done at baseline, after 3 months and after 6 months.
In the current study the mean age of the study population was 48.75±10.07 years. CTRCD occurred in 24 patients (25.5%) with mean EF by Simpson`s method 59.29±3.50 % at (T0), 49.54±5.63% at (T1), 45.79±4.49% at (T2). While in non-CTRCD patients the mean EF was 60.21±2.80% at (T0), 59.13±2.53% at (T1), 58.29±2.63% at (T2). RV systolic function impairment (S`<10 cm/s) was more prevalent occurring in 37 patients representing 39.4% of the study population. By univariate and multivariate regression analysis LV GLS at (T1) (cut-off value <-15% with relative 12.5% reduction from the baseline value) was a strong predictor of CTRCD, but combining LV GLS with RV GLS & RV FWLS was the strongest (AUC=0.947, sensitivity=91.67%, specificity=90%). The current study results are consistent with results of Arciniegas Calle et al., 2018. At Arciniegas Calle et al., 2018, it was concluded that Combining both RV GLS at T1 and LV GLS was the strongest predictor of cardiotoxicity (area under the curve[AUC], 0.91; sensitivity, 100%; specificity, 73%; P <.001). LV GLS at T1 (AUC, 0.85; cutoff, − 14.06; sensitivity, 91%; specificity, 83%; P =.003) was also a strong indicator of subsequent cardiotoxicity.
We aimed at highlighting the importance of studying the changes in RV mechanics during the period of chemotherapy as combining some of these data with LV strain variables gives us the best chance to predict CTRCD and detect it as early as possible, so we can change the chemotherapy regimen and start cardio-protective measures early and to detect patients based on their baseline data who are at risk of later development of CTRCD