A diagnostic index for predicting heart rate variability decline and prognostic value in newly diagnosed non-small cell lung cancer patients

Abstract

Background: Heart rate variability (HRV) is an important marker of autonomic nervous system function and cardiovascular health. Holter monitoring is a crucial method for evaluating HRV, but the procedure and result analysis are relatively complex. This study aims to develop a simplified diagnostic index for predicting HRV decline in newly diagnosed non-small cell lung cancer (NSCLC) patients and evaluate its prognostic value.

Methods: This retrospective cross-sectional study included 131 newly diagnosed NSCLC patients. Baseline characteristics were compared between normal HRV group and declined HRV group. Univariate and multivariate logistic regression analyses identified significant predictors of HRV decline. A diagnostic index was developed based on resting heart rate (RHR), serum sodium, and interleukin-6 (IL-6) and externally validated. Kaplan-Meier survival analysis assessed the prognostic value of the index.

Results: Patients with declined HRV had higher median RHR (84 b.p.m. vs. 70 b.p.m., p < 0.001), lower serum sodium (136.3 mmol/L vs. 138.7 mmol/L, p < 0.001), lower serum albumin (39 g/L vs. 41 g/L, p = 0.031), higher lactate dehydrogenase (LDH) (202 U/L vs. 182 U/L, p = 0.010), and higher IL-6 (11.42 pg/ml vs. 5.67 pg/ml, p < 0.001). Multivariate analysis identified RHR (OR = 3.143, p = 0.034), serum sodium (OR = 6.806, p < 0.001), and IL-6 (OR = 3.203, p = 0.033) as independent predictors of HRV decline. The diagnostic index, with an area under the curve (AUC) of 0.849, effectively predicted HRV decline. ROC analysis of the external validation data demonstrated an AUC of 0.788. Survival analysis showed that patients with a diagnostic index > 2 had significantly worse overall survival (log-rank p < 0.001).

Conclusions: The study identified key clinical parameters that predict HRV decline in newly diagnosed NSCLC patients. The developed diagnostic index, based on RHR, serum sodium, and IL-6, effectively stratifies patients by HRV status and has significant prognostic value, aiding in early identification and management of high-risk patients.

Keywords: diagnostic index; heart rate variability; interleukin-6; non-small cell lung cancer; overall survival; resting heart rate; serum sodium.

Figure 1

Development and validation of the diagnostic index. (A) Assigned risk scores for RHR, serum sodium, and IL-6. RHR >82 b.p.m. is assigned a score of 1, and ≤82 b.p.m. is assigned a score of 0. Serum sodium ≤138.2 mmol/L is assigned a score of 2, and >138.2 mmol/L is assigned a score of 0. IL-6 >6.74 pg/ml is assigned a score of 1, and ≤6.74 pg/ml is assigned a score of 0. Total scores range from 0 to 4. (B) ROC curve for the diagnostic index. The diagnostic index > 2 had the best predictive effect, with an AUC value of 0.849, a sensitivity of 76.39%, and a specificity of 79.66%. RHR, resting heart rate; IL-6, interleukin-6; ROC, receiver operating characteristic; AUC, area under the curve.

Figure 2

Kaplan-Meier survival analysis based on HRV and diagnostic index. (A) Kaplan-Meier survival curves for OS in patients with normal HRV versus declined HRV. Patients with declined HRV had significantly worse survival outcomes (log-rank p = 0.016). (B) Kaplan-Meier survival curves for OS stratified by the diagnostic index. Patients with a diagnostic index >2 exhibited significantly poorer OS compared to those with a diagnostic index ≤2 (log-rank p < 0.001). HRV, heart rate variability; OS, overall survival.

Figure 3

Subgroup analysis of OS based on the diagnostic index. Patients with diagnostic index ≤ 2 demonstrated better OS than patients with diagnostic index > 2 in all subgroup analyses. No statistically significant difference in OS was observed between patients with a diagnostic index ≤ 2 and those with a diagnostic index >2 in aged <60 years subgroup and stage IV subgroup (p values of 0.054 and 0.056, respectively). Other subgroups had statistical significance (p < 0.05). OS, overall survival; HR, hazard ratio; CI, confidence interval.