Nonlinear heart rate variability biomarkers for gastric cancer severity: A pilot study

Identifying prognostic factors by affordable tools is crucial for guiding gastric cancer (GC) treatments especially at earlier stages for timing interventions. The autonomic function that is clinically assessed by heart rate variability (HRV) is involved in tumorigenesis. This pilot study was aimed to examine whether nonlinear indices of HRV can be biomarkers of GC severity. Sixty-one newly-diagnosed GC patients were enrolled. Presurgical serum fibrinogen (FIB), carcinoembryonic antigen (CEA), and carbohydrate antigen 19-9 (CA199) were examined. Resting electrocardiogram (ECG) of 5-min was collected prior to surgical treatments to enable the HRV analysis. Twelve nonlinear HRV indices covering the irregularity, complexity, asymmetry, and temporal correlation of heartbeat fluctuations were obtained. Increased short-range temporal correlations, decreased asymmetry, and increased irregularity of heartbeat fluctuations were associated with higher FIB level. Increased irregularity and decreased complexity were also associated with higher CEA level. These associations were independent of age, sex, BMI, alcohol consumption, history of diabetes, left ventricular ejection fraction, and anemia. The results support the hypothesis that perturbations in nonlinear dynamical patterns of HRV predict increased GC severity. Replication in larger samples as well as the examination of longitudinal associations of HRV nonlinear features with cancer prognosis/survival are warranted.