Author + information
- Published online November 5, 2018.
- Rafael B. Piveta, MD∗ (, )@rbpiveta,
- Ana Clara T. Rodrigues, MD, PhD,
- Marcelo L.C. Vieira, MD, PhD,
- Cláudio H. Fischer, MD, PhD,
- Tania R. Afonso, RN,
- Edgar Daminello, MD, PhD,
- Felipe M. Cruz, MD, PhD,
- Tatiana F.G. Galvão, MD, PhD,
- Marcelo Katz, MD, PhD, MHS and
- Samira S. Morhy, MD, PhD
- ↵∗Hospital Israelita Albert Einstein, Av. Albert Einstein 627/701, Morumbi, São Paulo, SP 05652-900, Brazil
Cancer therapy-related cardiac dysfunction (CTRCD) represents an important cause of morbidity and mortality; early detection along with cardioprotection are fundamental to improve prognosis (1). However, usual diagnostic parameters have low sensitivity, increasing interest for early markers of CTRCD (1). A 3-dimensional speckle tracking echocardiography (3D-STE) has revealed more consistent data than a 2-dimensional (2D) technique and may prove to be more accurate in patients undergoing chemotherapy (2). This prospective study investigated myocardial deformation using 3D-STE in patients with breast cancer treated with low doses of anthracyclines to identify early markers of cardiotoxicity.
Patients >18 years of age, newly diagnosed with breast cancer, and scheduled for chemotherapy with anthracyclines were eligible. Exclusion criteria included previous chemotherapy or radiotherapy, inadequate echocardiographic imaging (>2 nonvisualized segments) and a left ventricular ejection fraction (LVEF) <55% before chemotherapy. Patients underwent a comprehensive echocardiogram and collection of ultrasensitive troponin I (US-TnI) during the following 3 stages: at baseline and after nonliposomal doxorubicin cumulative dosages of 120 and 240 mg/m2. We analyzed the LVEF (Simpson's method), 2D global longitudinal strain (GLS), and 2D midpapillary radial strain (RS); for 3D-STE, we measured 3D-GLS, 3D-global RS, global circumferential strain (3D-GCS), and global area strain (3D-GAS) along with rotation, twist, and torsion. Variables were compared among evaluation stages using generalized estimating equations with normal distribution and identity link function followed by multiple Bonferroni comparisons. Due to the asymmetric distribution, for US-TnI, the logarithmic function was used.
A total of 47 patients were eligible for the study, with 3 exclusions (2 due to inadequate echocardiographic images and 1 noncardiac-related death). Forty-four female patients 48.7 ± 10.8 years of age were evaluated, with results summarized in Table 1. The mean LVEF was unchanged during treatment; however, the 2D-GLS decreased only after the 240 mg/m2 dose (p = 0.001), with no changes after a lower dosage of doxorubicin (120 mg/m2). The 2D-RS was similar during both stages. After a dose of 240 mg/m2 of doxorubicin, 3D-STE detected changes in most myocardial deformation parameters: 3D-GLS, 3D-global RS, 3D-GCS, and 3D-GAS; no changes were observed for rotation, torsion, or twist. After a lower dose of doxorubicin, the only parameters that changed were 3D-GCS (p = 0.021) and 3D-GAS (p < 0.001). Twenty patients (45%) presented with a US-TnI of >34 pg/ml after a doxorubicin dose of 240 mg/mg2 (p = 0.001); however, a lower doxorubicin dose produced no change in US-TnI.
Myocardial deformation analysis using 3D-STE has been shown to be reliable and reproducible to assess LV mechanics in various clinical conditions (2). However, this technique has been poorly explored in the scenario of CTRCD. In the present study, after a cumulative dosage of 240 mg/m2 of doxorubicin, changes in almost all 3D-STE indexes were observed, implying that abnormalities are present in all directions of myocardial contraction. Interestingly, 3D-GCS and -GAS were the only parameters that changed at an earlier stage, suggesting improved sensitivity for early detection of chemotherapy-related changes. Recent research has evaluated patients under treatment with anthracyclines, demonstrating the potential superiority of 3D-GCS and -GAS compared with other echocardiographic parameters for the subclinical diagnosis of cardiotoxicity (3); however, these patients were evaluated after a greater cumulative anthracyclic dosage, with the association of traztuzumab or radiotherapy. Changes in torsion and twist rate were observed with the 2D technique after anthracyclic treatment (4); however, 3D-STE analysis did not confirm these findings. Finally, despite its confirmed value after a high dosage of anthracyclines, US-TnI was not useful to detect early changes in patients with breast cancer.
Some limitations must be pointed out, namely, the small sample size, research performed in a single center, and the low 3D-STE volume rate (20 to 30 volumes/s). Moreover, long-term follow-up is necessary to determine whether 3D-STE changes might correlate with clinical outcomes or subsequent LVEF reduction.
In conclusion, this analysis of myocardial mechanics using 3D-STE in patients with breast cancer treated with anthracyclines detected early changes in 3D-GCS and -GAS after very low doses of doxorubicin, representing a promising technique for CTRCD.
Please note: The authors have reported that they have no relationships relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
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