Early Change in Area Strain Detected by 3D Speckle Tracking Is Associated With Subsequent Cardiotoxicity in Patients Treated With Low Doses of Anthracyclines

Abstract

Objective: To evaluate the prognostic impact of the parameters of myocardial deformation using three-dimensional speckle tracking echocardiography (3DSTE) in patients with breast cancer who underwent chemotherapy with low doses of anthracyclines.

Background: Chemotherapy-related cardiotoxicity has an important prognostic impact on cancer survivors. Three-dimensional STE has revealed more consistent data than two-dimensional techniques and may represent a more accurate tool in the evaluation of myocardial function in patients who underwent chemotherapy.

Methods: We evaluated patients with breast cancer who were treated with anthracyclines (associated or not with trastuzumab) in five stages: baseline, after cumulative doses of 120 and 240 mg/m² of doxorubicin, and then, after 6 months and at least 1 year after anthracyclines. Ultrasensitive troponin I (US-TnI) and a standard echocardiography study were performed at each stage. We analyzed left ventricular ejection fraction (LVEF) by Simpson's method, two-dimensional speckle tracking (2DSTE) with longitudinal and radial strain values, and 3DSTE with longitudinal, radial, and circumferential strain as well as twist, torsion, rotation, and three-dimensional global area strain (3DGAS). Cardiotoxicity was defined as a decrease in LVEF by more than 10 percentage points to a value lower than 53%.

Results: We evaluated 51 female patients who were aged 50.6 ± 11 years. After the cumulative dose of 240 mg/m² of doxorubicin, US-TnI was increased (>34 pg/ml) in 21 patients (45%, p > 0.001), LVEF remained unchanged (p = 0.178), while 2DSTE longitudinal strain was decreased (from -17.8% to -17.1%, p < 0.001) and 3DSTE detected changes in longitudinal, radial, circumferential, and area strain. After a lower cumulative dose of doxorubicin (120 mg/m²), 3DGAS (p < 0.001) was the only parameter that was changed. In the follow-up, 7 (13%) patients presented a decrease in LVEF. Three-dimensional GAS early changed to abnormal values was the only variable associated with a subsequent decrease in LVEF (definitive cardiotoxicity).

Conclusion: In patients with breast cancer, 3DSTE detected early changes in area strain after very low doses of doxorubicin. The 3DGAS early changed to abnormal values was associated with a subsequent decrease in LVEF, representing a promising technique to predict chemotherapy-induced cardiomyopathy.

Keywords: 3D speckle tracking; 3D strain; cardiotoxicity; chemotherapy; echocardiography.

Figure 1

Stages of evaluation.

Figure 2

Changes in left ventricle ejection fraction (LVEF) during the treatment. Compared to baseline, LVEF did not change during the chemotherapy with doxorubicin (p = 0.178).

Figure 3

Changes in global longitudinal strain derived from the two-dimensional speckle tracking echocardiography. Compared to baseline, two-dimensional global longitudinal strain (2DGLS) did not change earlier, after 120 mg/m² of doxorubicin (p < 0.103). There was a decrease in 2DGLS after 240 mg/m² of doxorubicin compared to baseline (p < 0.001). However, the relative change of 2DGLS was mild, with no patient presenting criteria for the diagnosis of subclinical cardiotoxicity.

Figure 4

Changes in global area strain derived from the three-dimensional speckle tracking echocardiography. Compared to baseline there was a decrease in three-dimensional global area strain (3DGAS) after a lower cumulative dose of doxorubicin (120 mg/m²; p < 0.001). There was a decrease in 3DGAS after 240 mg/m² dose of doxorubicin compared to baseline (p < 0.001).

Figure 5

Changes in global area strain derived from the three-dimensional speckle tracking echocardiography. Patient with breast cancer undergoing chemotherapy with doxorubicin. In the baseline evaluation, pre-chemotherapy, left ventricular ejection fraction (LVEF): 0.70 and 3DGAS: −43.5% (A,B). After a low cumulative dose of doxorubicin (120 mg/m²), LVEF: 0.63 was observed (with reduction, but still preserved) and a significant decrease in three-dimensional global area strain (3DGAS) to −36.2% (C,D). Six months after the end of chemotherapy with doxorubicin (total cumulative dose of 240 mg/m²), the LVEF dropped to 0.50 (E). GAS, global area strain; LVEF, Left ventricle ejection fraction.

Figure 6

Studies reporting the 3D speckle tracking echocardiography analysis in cancer patients undergoing chemotherapy. GAS, global area strain; GCS, global circumferential strain; LVEF, Left ventricle ejection fraction. STE, speckle tracking echocardiography.