Cardiac Monitoring for Patients Undergoing Treatment With MEK Inhibitor Monotherapy
Abstract
Aberrant activation of the RAS-RAF-MEK-ERK signaling pathway contributes to numerous malignancies, congenital syndromes, and cardiovascular disorders, establishing MEK inhibitors (MEKi) as crucial therapeutic agents. MEKi demonstrate substantial clinical benefit as monotherapy (e.g., NF1-associated tumors) or combination therapy (e.g., melanoma, glioma, congenital RASopathies). Cardiovascular adverse events, primarily asymptomatic reductions in left ventricular ejection fraction (LVEF), have prompted intensive echocardiographic monitoring. Emerging evidence indicates that isolated mild LVEF decreases rarely progress to symptomatic heart failure, raising concerns about unnecessary treatment interruptions driven by overly rigorous imaging protocols. Integrating cardiac biomarkers into monitoring strategies could offer a more pragmatic approach, guiding echocardiographic evaluations based on biomarker elevation or symptoms. Expert recommendations advocate personalized, risk-adapted surveillance frameworks. High-risk patients include those with baseline cardiovascular conditions, abnormal biomarker profiles, or significant clinical symptoms. Normal-risk patients can be safely monitored clinically, reserving imaging for biomarker changes or symptom onset. Prospective studies should seek to validate these recommendations.