Evaluating the effect of PD-1 inhibitors on left ventricular function in lung cancer with noninvasive myocardial work

Abstract

Background The treatment of advanced lung cancer has been revolutionized by immune checkpoint inhibitors (ICIs) in recent years, largely driven by programmed cell death-1 (PD-1) inhibitors. However, patients with lung cancer who are treated with PD-1 inhibitors are prone to immune-related adverse events (irAEs), especially cardiac adverse events. Noninvasive myocardial work is a novel technique used to assess left ventricular (LV) function, which can effectively predict myocardial damage. Here, noninvasive myocardial work was used to evaluate changes in LV systolic function during PD-1 inhibitor therapy and to assess ICIs-related cardiotoxicity. Methods From September 2020 to June 2021, 52 patients with advanced lung cancer in the Second Affiliated Hospital of Nanchang University were prospectively enrolled. In total, 52 patients underwent PD-1 inhibitor therapy. The cardiac markers, noninvasive LV myocardial work, and conventional echocardiographic parameters were measured at pretherapy (T0) and posttreatment after the first (T1), second (T2), third (T3), and fourth (T4) cycles. Following this, the trends of the above parameters were analyzed using analysis of variance with repeated measures and the Friedman nonparametric test. Furthermore, the relationships between disease characteristics (tumor type, treatment regimen, cardiovascular risk factors, cardiovascular drugs, and irAEs) and noninvasive LV myocardial work parameters were assessed. Results Throughout the follow-up, the cardiac markers and conventional echocardiographic parameters showed no significant changes. Based on the normal reference ranges, patients with PD-1 inhibitor therapy had increased values of LV global waste work (GWW) and decreased global work efficiency (GWE) that began at T2. Compared with T0, GWW increased from T1 to T4 (42%, 76%, 87%, and 87%, respectively), while global longitudinal strain (GLS), global work index (GWI), and global constructive work (GCW) decreased in varying degrees (P<0.001). Most of the disease characteristics had no effect on the LV myocardial work parameters; however, the numbers of irAEs were closely associated with GLS (P=0.034), GWW (P<0.001), and GWE (P<0.001). Patients with 2 or more irAEs had higher values of GWW and lower GLS and GWE. Conclusions Noninvasive myocardial work can accurately reflect myocardial function and energy utilization in patients with lung cancer who are undergoing PD-1 inhibitor treatment and may thus benefit the management of patients with ICIs-related cardiotoxicity.

Multimodality Cardiovascular Imaging of Cardiotoxicity Due to Cancer Therapy

“…Indices of myocardial work, such as global work index (GWI), global constructive work (GCW), and global work efficiency (GWE), appear to be early and sensitive markers of progression towards cardiotoxicity in patients undergoing anthracycline therapy with or without trastuzumab [40][41][42]. There is also emerging evidence suggesting that myocardial work reflects myocardial function and energy utilization in patients receiving PD-1 inhibitor treatment for lung cancer [43]. However, further research is needed to establish the routine clinical use of myocardial work in managing cardiotoxicity.…”