Myocardial work brings a new insight into left ventricule remodelling in cardiooncology patients
Authors: Ferreira V , Cruz Coutinho M , Moura Branco L , Galrinho A , Timoteo AT , Rio P , Almeida Morais L , Aguiar Rosa S , Duarte Oliveira S , Leal A , Castelo A , Garcia Bras P , Reis JP , Cruz Ferreira R 
Published: February 2021

Abstract

Funding Acknowledgements
Type of funding sources: None.

Introduction
Serial echocardiographic assessment of 2D left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) is the gold standard screening method for cancer therapeutics-related cardiac dysfunction (CTRCD). Non-invasive left ventricular (LV) pressure-strain loop (PSL) provides a novel method of quantifying myocardial work (MW) with potential advantages, as it incorporates measurements of myocardial deformation and LV pressure.

Purpose
To evaluate the impact of cardiotoxic treatments in MW indices.

Methods
Prospective study of female breast cancer patients (P) submitted to therapy (TH) who underwent serial monitoring by 2D, 3D transthoracic echocardiography (TTE) and concomitant blood pressure assessment. P were evaluated at T0, T1 and T2 (before, ≥6 and ≥12 months after starting TH). PSL analysis allowed the calculation of the following indices: Global Work Index (GWI), Global Constructive Work (GCW), Global Work Waste (GWW) and Global Work Efficiency (GWE). CTRCD was defined as an absolute decrease in 2D LVEF &gt; 10% to a value &lt; 54% or a relative decrease in 2D GLS &gt; 15%, according to literature.

Results
122 patients (mean age 54.7 ± 12.0 years), mostly treated with anthracyclines (77.0%, cumulative dose 268.6 ± 71.8mg/m2), anti-HER (75.4%) and radiotherapy (77.0%) were included. 2D and 3D LVEF were significantly reduced during TH, however remaining within the limits of normality (2D LVEF T0-T1 64.2 ±7.6 vs 61.1 ± 8.2%, p = 0.006 and 3D LVEF T0-T1 60.2 ± 6.7 vs 56.9 ±6.3%, p = 0.022). 2D GLS was also more impaired at T1 (-19.8 ± 2.7% vs -18.5 ± 3.0%, p = 0.003).
All MW indices were significantly reduced at T1 compared to baseline (GWI 1756.9 ± 319.2 vs 1614.3 ± 338.5mmHg%, p = 0.005; GCW 2105.6 ± 352.0 vs 1970.5 ± 376.2 mmHg%, p = 0.015; GWW 121.1 ± 66.6 vs 161.1 ± 84.1 mmHg%, p = 0.001; GWE 93.5 ± 3.1 vs 91.1 ± 4.5%, p = 0.001). Between T1 and T2 no statistical difference was found but a partial recovery of parameters was observed when comparing T2 to T0 (GWI (T2) 1650.6 ± 357.5 mmHg%, p = 0.035; GCW (T2) 2013.3 ± 379.3 mmHg%, p = 0.086; GWW (T2) 148.0 ± 85.0 mmHg%, p = 0.02 and GWE (T2) 92.0 ± 4.7%, p = 0.012).
During a mean follow-up of 14.9 ± 9.3 months, 36 patients (29.5%) developed CTRCD. P presenting CTRCD revealed a significant decrease in GWI and GWE at T1 comparing with women without CTRCD (GWI 1.8 ± 21.6 vs -14.2 ± 18.5%, p = 0.004 and GWE -1.0 ±3.0 vs -3.6 ±3.9%, p = 0.005). GWW had a substantially increase at T1 in P with cardiotoxicity (27.6 ± 76.3% vs 64.1 ± 68.0%, p = 0.051).

Conclusion
Left ventricular systolic function study with MW showed a reduction in cardiac performance with a peak at 6 months from the start of chemotherapy and partial recovery after term. Assessment of myocardial deformation parameters, namely MW, proved to be a useful tool for a better characterisation of cardiac remodelling, and could enhance patient selection for cardioprotective therapeutics.
Abstract Figure. TTE parameters