Dynamic Integrated Backscatter Detects Radiotherapy-induced Cardiac Changes Better than Strain Analysis - A Prospective Three-year Study.

BACKGROUND/AIM: Radiotherapy (RT) related myocardial changes were analyzed by deformation imaging echocardiography in this study. PATIENTS AND METHODS: Ninety-nine breast cancer patients were studied at baseline, after chemotherapy, after RT, and three years after RT (3Y). Eighty patients received RT only, and twenty patients had right-sided breast cancer. Echocardiography included cyclic variation of the integrated backscatter in the septum (sCV) and posterior wall (pCV), global longitudinal strain (GLS), and left ventricular ejection fraction (LVEF). RESULTS: In patients with left-sided breast cancer, sCV declined from 11.3±3.3 dB at baseline to 10.3±2.9 dB after RT (p=0.001). No changes were observed after chemotherapy (p=0.211) or in patients with right-sided breast cancer after RT (p=0.977). No other parameters declined after RT. The decline in sCV was independently associated with the left anterior descending coronary artery radiation dose (ß=-0.290, p=0.020). CONCLUSION: In contrast to other parameters, sCV correlated with heart radiation dose.

A Higher Mean Heart Radiation Dose Induces Higher Frequency of Multiple Cardiac Changes.

BACKGROUND/AIM: Radiotherapy (RT) induces late changes in all cardiac structures. Most studies of early changes focus on individual parameters. PATIENTS AND METHODS: Data from eighty early-stage breast cancer patients at baseline, post-RT and three-year follow-up visit were assessed prospectively. Changes in ten cardiac parameters were collected including electrocardiogram (ECG), echocardiography, and biomarkers. A percentage of abnormal changes was calculated. RESULTS: The mean heart radiation dose (Dmean) was independently associated with the increased incidence of changes post-RT (ß=0.403, p<0.001) and at the three-year follow-up (ß=0.353, p=0.001). Each 1-Gray increase in Dmean increased the cardiac changes by 3.7% (95%CI=1.9-5.6%) after RT and 3.1% (95%CI=1.3, 4.9%) at the three-year follow-up. CONCLUSION: A higher cardiac radiation dose was independently associated with a higher incidence of changes in cardiac parameters. Multiparameter changes imply that the early phase after RT is already characterized by several overlapping cardiac changes.

3-Year Follow-Up of Radiation-Associated Changes in Diastolic Function by Speckle Tracking Echocardiography.

BACKGROUND: Radiation therapy (RT) results in myocardial changes consisting of diffuse fibrosis, which may result in changes in diastolic function. OBJECTIVES: The aim of this study was to explore RT-associated changes in left ventricular (LV) diastolic function. METHODS: Sixty chemotherapy-naive patients with left-sided, early-stage breast cancer were studied with speckle tracking echocardiography at 3 time points: prior to, immediately after, and 3 years after RT. Global and regional early diastolic strain rate (SRe) were quantified, as were parameters of systolic function. RESULTS: Regional changes in SRe, particularly the apical and anteroseptal segments, were observed over time and were more evident than global changes. The apical SRe declined from a median of 1.24 (interquartile range: 1.01 to 1.39) s-1 at baseline to 1.02 (interquartile range: 0.79 to 1.15) s-1 at 3 years of follow-up (p < 0.001). This decline was associated with the left ventricular maximal radiation dose (ß = 0.36, p = 0.007). The global SRe was <1.00 s-1 (SRedep) in 11 (18.3%) patients at baseline, 21 (35%) patients (p = 0.013) post-RT, and 17 (28.3%) patients (p = 0.051) at 3 years. SRedep post-RT was independently associated with baseline cardiac abnormalities (odds ratio: 0.26; 95% confidence interval: 0.08 to 0.84; p = 0.025); SRedep at 3 years of follow-up was associated with the baseline Charlson comorbidity index (odds ratio: 2.36; 95% confidence interval: 1.17 to 4.77; p = 0.017). Diastolic function abnormalities were evident even in patients with preserved global longitudinal strain at 3 years. CONCLUSIONS: RT resulted in changes in the SRe in the apical and anteroseptal segments over 3 years of follow-up. Changes in SRe apical segments were present even in patients with preserved systolic function and were independently associated with RT dose and cardiovascular comorbidities.

Left Ventricular Speckle Tracking Echocardiography Changes Among Early-stage Breast Cancer Patients Three Years After Radiotherapy.

BACKGROUND/AIM: Chest radiotherapy (RT) doubles late cardiac mortality. This study aimed to evaluate the evolution of cardiac changes in speckle tracking echocardiography during a three-year follow-up. MATERIALS AND METHODS: This prospective study included 81 chemotherapy-naïve early-stage breast cancer patients who were evaluated at baseline, immediately after RT and three years after RT. Sixty-one patients had left-sided (LSBC) and 20 right-sided breast cancer (RSBC). RESULTS: Global longitudinal strain (GLS) declined from baseline -18.0±3.3% to -17.0±3.0% (p=0.015) at the three-year follow-up examination. A decline over 15% (GLS15) was observed in 19 (27%) patients. GLS15 was independently associated with aromatase inhibitor use (ß=-1.977, p=0.001). In regional analysis, patients with LSBC had apical strain decline by 3.2±5.5% (p<0.001) and patients with RSBC showed basal rotation decline by 1.8° (-0.2°, 3.8°) (p=0.030). CONCLUSION: Even contemporary RT induced progressive global and regional decline in speckle tracking analysis. The regional changes complied with RT fields.

Radiotherapy-induced Early ECG Changes and Their Comparison with Echocardiography in Patients with Early-stage Breast Cancer.

BACKGROUND: Early electrocardiogram (ECG) changes after breast cancer radiotherapy (RT) have been reported, but their characteristics and associated factors are largely unknown. This study aimed to explore early RT-induced ECG changes and to compare them with echocardiography changes. MATERIALS AND METHODS: Sixty eligible patients with chemotherapy-naïve left-sided and 20 with right-sided breast cancer were evaluated with echocardiography, blood samples and ECG before and after RT. RESULTS: RT-induced ECG changes in the anterior leads. T-Wave changes were most frequent. T-Wave decline was associated independently with patient age (ß=-0.245, p=0.005), mean heart radiation dose (ß=1.252, p=0.001) and global systolic strain rate change (ß=7.943, p=0.002). T-Wave inversion was associated independently with mean heart radiation dose (ß=0.143, p<0.001), global longitudinal strain change (ß=0.053, p=0.017) and posterior calibrated integrated backscatter (ß=-0.022, p=0.049). CONCLUSION: RT-induced ECG changes were prevalent and associated with functional and structural changes in echocardiography. ECG could be used for post-RT cardiac screening.

Associations between ECG changes and echocardiographic findings in patients with acute non-ST elevation myocardial infarction.

BACKGROUND: ST segment depression (STD) and T wave inversion (TWI) are typical electrocardiographic (ECG) findings in non-ST elevation myocardial infarction (NSTEMI). In ST elevation myocardial infarction, ST changes represent transmural ischemia. The pathophysiological mechanisms of the ECG changes in NSTEMI are unclear. PURPOSE: We studied the associations between ECG and the echocardiographic findings in NSTEMI patients. METHODS: Twenty patients with acute NSTEMI were recruited during their hospital stay. A comprehensive echocardiography study was performed. The findings were compared with blinded ECG analyses. RESULTS: Nine (45%) patients had STD, and 16 (85%) patients had TWI. In multivariable analysis, STD was independently associated with a lower global early diastolic strain rate (ß=-5.061, p=0.033). TWI was independently associated with lower circumferential strain (ß=0.132, p=0.032). CONCLUSIONS: The typical ECG changes in NSTEMI patients were associated with subtle echocardiographic changes. STD was related to changes in diastolic function, and TWI was associated with systolic deterioration.

Detection of early radiotherapy-induced changes in intrinsic myocardial contractility by ultrasound tissue characterization in patients with early-stage breast cancer.

BACKGROUND: Increased cardiovascular morbidity and mortality are major late complications after radiotherapy (RT) in the thoracic region. Ultrasound tissue characterization (UTC) is a noninvasive method for the identification of myocardial changes. The aim of this prospective clinical trial was to assess whether the analysis of cyclic variation of integrated backscatter (CVIBS) can detect early RT-induced myocardial alterations. METHODS: Seventy-three eligible patients with early-stage breast cancer were evaluated before and immediately after adjuvant RT. Twenty and 53 patients had right-sided and left-sided breast cancer, respectively. None of the patients received chemotherapy. Comprehensive echocardiographic examination included three-dimensional (3D) measurements and UTC analysis of the left ventricular (LV) septum and posterior wall. RESULTS: RT reduced CVIBS in a dose-dependent manner. The mean heart radiation dose over two gray (Gy) reduced the septal CVIBS from 12.0±3.4 to 9.6±2.5 dB (P<.001) and the posterior wall CVIBS from 12.8±2.7 to 11.3±2.4 dB (P=.007). The CVIBS remained unchanged when the mean heart RT dose was below 2 Gy. Multivariate analysis showed an independent association with a change in septal CVIBS and the use of aromatase inhibitor (ß=2.986, P=.001) and body mass index (ß=-0.241, P=.014). The posterior values were worse with higher mean lung dose (ß=-.485, P=.018) and with nonsmoking status (ß=-2.411, P=.009). Echocardiography parameters showed increased myocardial mass but conventional measurements of the LV systolic function remained unchanged. CONCLUSIONS: Cyclic variation of integrated backscatter analysis seems to be a sensitive method to detect early RT-induced myocardial changes. Hence, it may be useful in screening of patients needing closer follow-up.

Radiotherapy-induced global and regional differences in early-stage left-sided versus right-sided breast cancer patients: speckle tracking echocardiography study.

Radiotherapy (RT) to the thoracic region increases late cardiovascular morbidity and mortality. The impact of breast cancer laterality on cardiac function is largely unknown. The aim of this prospective study was to compare RT-induced changes in left-sided and right-sided breast cancer patients using speckle tracking echocardiography (STE). Sixty eligible patients with left-sided breast cancer and 20 with right-sided breast cancer without chemotherapy were evaluated prospectively before and early after RT. A comprehensive echocardiographic examination included three dimensional measurements and STE of the left ventricle (LV). The global longitudinal strain (GLS) was reduced from -18.3 ± 3.1 to -17.2 ± 3.3% (p = 0.003) after RT in patients with left-sided breast cancer. Similarly, regional analysis showed a reduction in the apical strain from -18.7 ± 5.3 to -16.7 ± 4.9% (p = 0.002) and an increase in basal values from -21.6 ± 5.0 to -23.3 ± 4.9% (p = 0.024). Patients with right-sided breast cancer showed deterioration in basal anterior strain segments from -26.3 ± 7.6 to -18.8 ± 8.9% (p < 0.001) and in pulsed tissue Doppler by 0.825 [0.365, 1.710] cm/s (p < 0.001). In multivariable analysis, the use of aromatase inhibitor (ß = -2.002, p = 0.001) and decreased LV diastolic volume (ß = -0.070, p = 0.025) were independently associated with the decrease in GLS. RT caused no changes in conventional LV systolic measurements. RT induced regional changes corresponded to the RT fields. Patients with left-sided breast cancer experienced apical impact and global decline, whereas patients with right-sided breast cancer showed basal changes. The regional differences in cardiac impact warrant different methods in screening and in the follow-up of patients with left-sided versus right-sided breast cancer.

Detection of radiotherapy-induced myocardial changes by ultrasound tissue characterisation in patients with breast cancer.

Radiotherapy (RT) in the thoracic region is associated with an increased risk of late cardiovascular morbidity and mortality. Ultrasonic tissue characterisation (UTC) is a non-invasive method of identifying changes in myocardial tissue, such as increased fibrosis. The aim of this study was to assess whether UTC can detect early RT-induced myocardial alterations. Seventy-eight eligible patients with early stage breast cancer were evaluated before and immediately after RT. Twenty patients had right-sided and 58 left-sided breast cancer. None received chemotherapy. A comprehensive echocardiographic examination included 3D measurements and UTC of the right ventricular (RV) free wall, ventricular septum and left ventricular (LV) posterior wall. Integrated backscatter calibration was done for the pericardium (cpIBS) and LV cavity (ccIBS). RT for left-sided breast cancer was associated with increased echodensity in the UTC analysis. RV free wall and ventricular septum cpIBS increased from -15.0 ± 7.3 to -13.7 ± 7.9 dB (p = 0.079) and from -18.2 ± 5.1 to -16.0 ± 6.4 dB (p = 0.002), respectively. Likewise, ccIBS in the RV free wall increased from 20.4 ± 5.9 to 22.1 ± 5.6 dB (p = 0.046), and in the LV septum from 17.3 ± 5.2 to 19.8 ± 5.5 dB (p < 0.001). In 3D echocardiography, LV mass increased from 102 ± 18 to 107 ± 18 g (p = 0.005). Patients receiving RT for right-sided breast cancer did not display these changes. Left-sided RT increased myocardial echodensity, particularly in the structures receiving the highest radiation dose. Considering the progressive nature of the RT induced damage, these early changes may help us with individual risk stratification and serve as a tool for screening.

Early effects of adjuvant breast cancer radiotherapy on right ventricular systolic and diastolic function.

AIM: Reduced right ventricular (RV) systolic function correlates with poor prognosis in several heart diseases. The aim of this prospective single-Center study was to investigate whether conformal three-dimensional (3D) breast cancer radiotherapy impairs RV function. PATIENTS AND METHODS: Forty-nine patients with early-stage left-sided breast cancer underwent comprehensive two-dimensional (2D) echocardiography before and after radiotherapy. RV function was evaluated with tricuspid annular plane systolic excursion (TAPSE), pulsed tissue Doppler peak velocity at the lateral RV wall (S') and RV and venous flow analysis. RESULTS: Radiotherapy reduced TAPSE from 24.5 ± 4.0 mm to 22.4 ± 3.9 mm (p<0.001), S' from 12.7 ± 3.1 m/s to 12.2 ± 2.7 m/s (p=0.11) and pulmonary flow velocity time integral (VTI) from 16.6 ± 3.1 cm to 15.9 ± 2.3 cm (p=0.07), respectively. These changes were unrelated to changes in LV function. CONCLUSION: Modern radiotherapy reduced RV systolic function. As a readily-available and sensitive measurement, TAPSE is as a practical tool for detection of radiotherapy-induced cardiac changes.