Pre-procedural Heart Rate Variability Predicts Recurrence-Free Survival in Hepatocellular Carcinoma after Microwave Ablation: A Retrospective Cohort Study with Proteomic Exploration

Background & Aims : Heart rate variability (HRV) reflects autonomic function and has prognostic value in several cancers. We evaluated whether pre‑procedural HRV predicts recurrence‑free survival (RFS) after microwave ablation (MWA) for hepatocellular carcinoma (HCC). Methods : This retrospective cohort included 101 HCC patients who underwent MWA (2021‑2024). Time‑domain HRV parameters (SDNN, RMSSD) were derived from pre‑procedural 10‑second ECGs. RFS was assessed by Kaplan‑Meier and multivariable Cox regression. Exploratory serum proteomics was performed in a matched subset (n=25) as a hypothesis‑generating analysis. Results : Over a median follow‑up of 12.0 months, 44 patients (43.6%) relapsed. Multivariable Cox regression confirmed SDNN ≥18.59 ms as an independent predictor of prolonged RFS (HR=0.384, 95%CI: 0.197‑0.752, P= 0.005), along with CRP (HR=1.058, 95%CI: 1.025‑1.092, P= 0.001) and recurrent tumor status (HR=2.407, 95%CI: 1.176‑4.926, P= 0.016). In exploratory proteomics (n=25), the high‑HRV group showed enrichment of proteins annotated to extracellular matrix organization and coagulation pathways, and relative downregulation of glycolysis/hypoxia pathway proteins; these associations require validation in independent cohorts. Conclusions : Higher pre‑procedural SDNN is independently associated with prolonged RFS after MWA for HCC. This simple, non‑invasive metric from routine ECGs may serve as a complementary prognostic biomarker to identify high‑risk patients.