Myocardial work as a tool for detecting subclinical cardiac dysfunction related to cancer therapy

Background The current role of global longitudinal strain (GLS) in diagnosing subclinical cardiac damage caused by anticancer drugs is well-established. However, there are some limitations associated with strain, such as its dependence on hemodynamic loading conditions. Purpose Our study aimed to explore the effectiveness of non-invasive myocardial work indices (MWI) derived from pressure–strain analysis for early cardiotoxicity diagnosis. Methods We included 80 patients (85% female) with solid tumors undergoing anthracycline ± trastuzumab ± paclitaxel chemotherapy. Patients underwent evaluation by 2D/3D echocardiography, measuring left ventricular ejection fraction (LVEF), GLS and MWI [global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE)] at baseline and after one, three, six and twelve moths post chemotherapy initiation. Results During follow-up, 20 patients (25% of patients) developed subclinical cardiac dysfunction or mild asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), defined as a relative decrease ≥15% in GLS from baseline, without a significant reduction in LVEF (threshold of 50%). In all patients, after chemotherapy initiation, GWE decreased and GWW increased significantly, as early as one month (p <0.05), while the other echocardiographic indices did not show significant changes. In patients who developed cardiotoxicity, GWE values were significantly reduced compared to patients who did not develop cardiotoxicity, at 1 month, 3 months, 6 months, and 12 months (all p <0.05), while other MWI did not show significant differences. Patients who developed cardiotoxicity, in the echocardiographic control prior to the development of mild asymptomatic CTRCD, showed significantly reduced GWE values compared to baseline values (90.1 ± 0.9% vs 93.7 ± 2.4%, p = 0.001); no significant changes were observed in the other MWI. Furthermore, patients who developed cardiotoxicity at the time of developing subclinical dysfunction showed a significant reduction in GWE (89.4 ± 0.9 vs 93.7 ± 2.4, p = 0.001) and GCW (1999 ± 366 mmHg% vs 2137 ± 374 mmHg%, p <0.05) compared to baseline values; no significant changes were observed in the other MWI. Conclusion MWI changes during chemotherapy are significant and occur early (reduced GWE, increased GWW). GWE appeared to decrease early in patients who developed subclinical cardiac dysfunction, even before a ≥15% decrease in GLS from baseline. An approach that includes both GLS and MWI could be useful for the early identification of subclinical cardiotoxicity. Including more patients might help identify a possible MWI cutoff that predicts, even earlier than GLS, subclinical cardiotoxicity.MWI in patients developing CTRCD A patient developing CTRCD