Longitudinal Evaluation of Immune Checkpoint Inhibitor‐Induced Fatigue Syndrome by Rest, Stress, and Speckle‐Tracking Strain Echocardiography

BACKGROUND: Immune checkpoint inhibitor (ICI) anti-tumor therapy is commonly associated with reports of significant fatigue. Whether ICI-induced fatigue is linked to subclinical cardiac toxicity is not well understood. METHODS: We performed a prospective observational study to monitor cardiac function following initiation of ICI in cancer patients. Rest and staged exercise stress transthoracic echocardiograms (TTE) were captured at baseline, 3 and 6 months after ICI initiation. RESULTS: Thirteen patients completed baseline testing, of whom 10 completed 3 month testing and 8 completed 6 month testing. Patients had elevated fatigue as per Common Terminology Criteria for Adverse Events (CTCAE) criteria and FACIT-Fatigue subscale scores (47.5 [42.5-52] vs. 47 [38-48], p = 0.001). Among resting echocardiographic parameters, left ventricular (LV) outflow tract velocity time integral (VTI) was reduced at 6 months (22.6 cm [21.2-24.5] vs. 19.8 cm [17.2-21.2], p = 0.001), albeit still within normal range. Measures of biventricular size and systolic function, along with LV global longitudinal strain (GLS) and LA global strain, were not significantly changed. Among exercise parameters, peak heart rate was reduced at 6 months (143.4 bpm [128.5-153.5] vs. 123.5 [110.2-130.8], p = 0.048); of those who completed 6 month testing, two (29%) were unable to achieve the previous peak stage of exercise. CONCLUSIONS: In patients starting ICI, statistically-significant reductions in cardiac systolic function (LVOT VTI) and peak HR were observed, with nearly one-third unable to achieve peak exercise at 6 months. This finding, combined with reported fatigue and lack of changes to biventricular systolic functional measures, suggests induced functional cardiac limitations are due to deconditioning, rather than cardiotoxicity.