Myocardial work and atrial strain for the early detection of subclinical cardiac dysfunction in bevacizumab treated colorectal cancer patients

Background Bevacizumab, a monoclonal antibody inhibitor of vascular endothelial growth factor (VEGF), can cause commonly left ventricular systolic dysfunction.The current role of echocardiography global longitudinal strain (GLS) in diagnosing subclinical cardiac damage caused by anticancer drugs is well-established. However, there is currently no data on the possible role of myocardial work indices (MWI) and left atrial (LA) strain in the early detection of bevacizumab-induced cardiac dysfunction. Purpose Our study aimed to explore the effectiveness of MWI derived from pressure–strain analysis and LA strain for early detection of cardiac dysfunction in patients with colorectal cancer treated with bevacizumab. Methods We included 42 patients (65.1 ± 7.5 years/old, 70% male) with metastatic colorectal cancers undergoing bevacizumab in combination with non-anthracycline-based chemotherapy (5-fluorouracil/ folinic acid plus oxaliplatin, FOLFOX i.v.). Patients underwent evaluation by 2D/3D echocardiography, measuring left ventricular ejection fraction (LVEF), LA Volume index (LAVi), GLS and MWI [global work index (GWI), global constructive work (GCW), global wasted work (GWW) and global work efficiency (GWE)] and LA reservoir longitudinal strain at baseline, after three and six moths post bevacizumab initiation. Results At six months, 8 patients (19% 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 bevacizumab initiation, GWE decreased and GWW increased significantly, both at three and six months (p <0.05), while there was no difference in the other echocardiographic parameters. There was no significant difference between baseline values of MWI and LA strain in patients who developed cardiotoxicity and those who did not. However, patients who developed cardiotoxicity showed significantly reduced values of GWE (p=0.001) and LA strain (p=0.001) compared to those who did not develop cardiotoxicity, at both three and six months. Patients who developed CTRCD at six months showed significantly reduced GWE (p=0.001) and LA strain (p=0.001) compared to baseline values, at both three months and six months. Conclusion MWI changes during bevacizumab therapy are significant and occur early (reduced GWE, increased GWW). GWE and LA strain 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, MWI and LA strain could be useful for the early identification of subclinical cardiotoxicity. Including more patients might help identify a possible MWI and LA strain cutoff that predicts, even earlier than GLS, subclinical cardiotoxicity in patient with metastatic colorectal cancers undergoing bevacizumab.GWE & LAstrain in pts with/without CTRCD MWI & LA strain in pts developing CTRCD