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Background: Prior research suggests that autonomic modulation investigated by heart rate variability (HRV) might act as a novel predictive biomarker for cancer prognosis, such as in breast cancer and pancreatic cancer. It is not clear whether there is a correlation between autonomic modulation and prognosis in patients with extensive-stage small cell lung cancer (ES-SCLC). Therefore, the purpose of the study was to examine the association between short-term HRV, deceleration capacity (DC) and acceleration capacity (AC) of heart rate and overall survival in patients with ES-SCLC. Methods: We recruited 40 patients with ES-SCLC, and 39 were included in the final analysis. A 5-min resting electrocardiogram of patients with ES-SCLC was collected using a microelectrocardiogram recorder to analyse short-term HRV, DC and AC. The following HRV parameters were used: standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD). Overall survival of patients with ES-SCLC was defined as time from the date of electrocardiogram measurement to the date of death or the last follow-up. Follow-up was last performed on 07 June 2023. There was a median follow-up time of 42.2 months. Results: Univariate analysis revealed that the HRV parameter SDNN, as well as DC significantly predicted the overall survival of ES-SCLC patients (all p < 0.05). Multivariate analysis showed that the HRV parameters SDNN (hazard ratio = 5.254, 95% CI: 1.817-15.189, p = 0.002), RMSSD (hazard ratio = 3.024, 95% CI: 1.093-8.372, p = 0.033), as well as DC (hazard ratio = 3.909, 95% CI: 1.353-11.293, p = 0.012) were independent prognostic factors in ES-SCLC patients. Conclusion: Decreased HRV parameters (SDNN, RMSSD) and DC are independently associated with shorter overall survival in ES-SCLC patients. Autonomic nervous system function (assessed based on HRV and DC) may be a new biomarker for evaluating the prognosis of patients with ES-SCLC.
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Background: Prior research suggests that cardiovascular autonomic dysfunction might be an early marker of cardiotoxicity induced by antitumor treatment and act as an early predictor of cardiovascular disease-related morbidity and mortality. The impact of thoracic radiotherapy on the parasympathetic and sympathetic nervous systems, however, remains unclear. Therefore, this study aimed to evaluate the short-term effects of thoracic radiotherapy on the autonomic nervous system, using deceleration capacity (DC), acceleration capacity (AC) of heart rate, and heart rate variability (HRV) as assessment tools. Methods: A 5 min electrocardiogram was collected from 58 thoracic cancer patients before and after thoracic radiotherapy for DC, AC, and HRV analysis. HRV parameters employed included the standard deviation of the normal-normal interval (SDNN), root mean square of successive interval differences (RMSSD), low frequency power (LF), high frequency power (HF), total power (TP), and the LF to HF ratio. Some patients also received systemic therapies alongside radiotherapy; thus, patients were subdivided into a radiotherapy-only group (28 cases) and a combined radiotherapy and systemic therapies group (30 cases) for additional subgroup analysis. Results: Thoracic radiotherapy resulted in a significant reduction in DC (8.5 [5.0, 14.2] vs. 5.3 [3.5, 9.4], p = 0.002) and HRV parameters SDNN (9.9 [7.03, 16.0] vs. 8.2 [6.0, 12.4], p = 0.003), RMSSD (9.9 [6.9, 17.5] vs. 7.7 [4.8, 14.3], p = 0.009), LF (29 [10, 135] vs. 24 [15, 50], p = 0.005), HF (35 [12, 101] vs. 16 [9, 46], p = 0.002), TP (74 [41, 273] vs. 50 [33, 118], p < 0.001), and a significant increase in AC (-8.2 [-14.8, -4.9] vs. -5.8 [-10.1, -3.3], p = 0.003) and mean heart rate (79.8 ± 12.6 vs. 83.9 ± 13.6, p = 0.010). Subgroup analysis indicated similar trends in mean heart rate, DC, AC, and HRV parameters (SDNN, RMSSD, LF, HF, TP) in both the radiotherapy group and the combined treatment group post-radiotherapy. No statistically significant difference was noted in the changes observed in DC, AC, and HRV between the two groups pre- and post-radiotherapy. Conclusion: Thoracic radiotherapy may induce cardiovascular autonomic dysfunction by reducing parasympathetic activity and enhancing sympathetic activity. Importantly, the study found that the concurrent use of systemic therapies did not significantly amplify or contribute to the alterations in autonomic function in the short-term following thoracic radiotherapy. DC, AC and HRV are promising and feasible biomarkers for evaluating autonomic dysfunction caused by thoracic radiotherapy.
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Background: Previous studies have shown that the predictive value of traditional linear (time domain and frequency domain) heart rate variability (HRV) for the survival of patients with advanced non-small cell lung cancer (NSCLC) is controversial. Nonlinear methods, based on the concept of complexity, have been used to evaluate HRV, providing a new means to reveal the physiological and pathological changes in HRV. This study aimed to assess the association between heartbeat complexity and overall survival in patients with advanced NSCLC. Methods: This study included 78 patients with advanced NSCLC (mean age: 62.0 ± 9.3 years). A 5-min resting electrocardiogram of advanced NSCLC patients was collected to analyze the following HRV parameters: time domain indicators, i.e., standard deviation of the normal-normal intervals (SDNN) and root mean square of successive interval differences (RMSSD); frequency domain indicators, i.e., total power (TP), low frequency power (LF), high frequency power (HF), and the ratio of LF to HF (LF/HF); nonlinear HRV indicators characterizing heartbeat complexity, i.e., approximate entropy (ApEn), sample entropy (SampEn), and recurrence quantification analysis (RQA) indexes: mean diagonal line length (Lmean), maximal diagonal line length (Lmax), recurrence rate (REC), determinism (DET), and shannon entropy (ShanEn). Results: Univariate analysis revealed that the linear frequency domain parameter HF and nonlinear RQA parameters Lmax, REC, and DET were significantly correlated with the survival of advanced NSCLC patients (all p < 0.05). After adjusting for confounders in the multivariate analysis, HF, REC, and DET were found to be independent prognostic factors for the survival of patients with advanced NSCLC (all p < 0.05). Conclusion: There was an independent association between heartbeat complexity and survival in advanced NSCLC patients. The nonlinear analysis method based on RQA may provide valuable additional information for the prognostic stratification of patients with advanced NSCLC and may supplement the traditional time domain and frequency domain analysis methods.
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Background: Previous studies have shown that heart rate variability (HRV) analysis is a sensitive indicator of chemotherapy-induced cardiotoxicity. However, most studies to date have observed long-term effects using long-term analyses. The main purpose of this study was to evaluate the acute effect of chemotherapy on the cardiac autonomic nervous system (ANS) in patients with cervical cancer (CC) by examining short-term HRV. Methods: Fifty patients with CC admitted to the Department of Gynecology and Oncology of the First Affiliated Hospital of Bengbu Medical College were enrolled in the study. Based on their chemotherapy regimens, the patients were divided into a DC group (docetaxel + carboplatin) and a TC group (paclitaxel + carboplatin). A 5-min resting electrocardiogram (ECG) was collected before and the day after chemotherapy: the time domain (standard deviation of normal-to-normal intervals (SDNN) and root mean square of successive differences (RMSSD)) and frequency domain (low-frequency power (LF), high-frequency power (HF), and (LF/HF)) parameters were analyzed, and the differences before and after chemotherapy were compared. Results: The results showed that SDNN, RMSSD and HF were significantly higher in the DC and TC groups after chemotherapy than before (p < 0.05, Cohen's d > 0.5). In addition, LF was significantly higher after TC than before chemotherapy (p < 0.05, Cohen's d > 0.3), and LF/HF was significantly lower after DC than before chemotherapy (p < 0.05, Cohen's d > 0.5). Conclusion: Chemotherapy combining taxane and carboplatin can increase the HRV of CC patients in the short term, and HRV may be a sensitive tool for the early detection of chemotherapy-induced cardiac ANS perturbations.
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Background: It has previously been shown that the time-domain characteristic of heart rate variability (HRV) is an independent prognostic factor for lung cancer patients with brain metastasis (LCBM). However, it is unclear whether the nonlinear dynamic features contained in HRV are associated with prognosis in patients with LCBM. Recurrence quantification analysis (RQA) is a common nonlinear method used to characterize the complexity of heartbeat interval time series. This study was aimed to explore the association between HRV RQA parameters and prognosis in LCBM patients. Methods: Fifty-six LCBM patients from the Department of Radiation Oncology, the First Affiliated Hospital of Bengbu Medical College, were enrolled in this study. Five-minute ECG data were collected by a mini-ECG recorder before the first brain radiotherapy, and then heartbeat interval time series were extracted for RQA. The main parameters included the mean diagonal line length (Lmean), maximal diagonal line length (Lmax), percent of recurrence (REC), determinism (DET) and Shannon entropy (ShanEn). Patients were followed up (the average follow-up time was 19.2 months, a total of 37 patients died), and the relationships between the RQA parameters and survival of LCBM patients were evaluated by survival analysis. Results: The univariate analysis showed that an Lmax of >376 beats portended worse survival in LCBM patients. Multivariate Cox regression analysis revealed that the Lmax was still an independent prognostic factor for patients with LCBM after adjusting for confounders such as the Karnofsky performance status (KPS) (HR = 0.318, 95% CI: 0.151-0.669, p = 0.003). Conclusion: Reduced heartbeat complexity indicates a shorter survival time in patients with LCBM. As a non-invasive biomarker, RQA has the potential for application in evaluating the prognosis of LCBM patients.
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Background: Evidence suggests that the risk of recurrence and death in patients with early cervical cancer (ECC) undergoing minimally invasive surgery is significantly higher than that in patients undergoing open surgery. However, the mechanisms underlying such a difference remain unclear. Heart rate variability (HRV) represents autonomic nerve activity, which is related to tumorgenesis and can be used as a prognostic indicator for various cancers. The main purpose of this study was to explore the difference in the effects of laparoscopic and open surgery on HRV in ECC patients. Methods: A total of 68 ECC (FIGO IA1 with lymphovascular space invasion -IIA2) patients undergoing radical hysterectomy for the first time (84% open group vs. 16% laparoscopic group) were included. A single-lead micro-ECG recorder was used to collect 5 min electrocardiograms 1 day before the operation and 3 days after the operation, and then HRV time domain and frequency domain indices were analyzed, including mean heart rate (MeanHR), maximum heart rate (MaxHR), minimum heart rate (MinHR), the standard deviation of all normal-to-normal intervals (SDNN), the root mean square of successive interval differences (RMSSD), very low-frequency power (VLF), low-frequency power (LF), high-frequency power (HF), total power (TP), and the ratio of LF to HF (LF/HF). Results: Heart rate (i.e., MeanHR, MaxHR, and MinHR) were significantly higher, and HRV (i.e., SDNN, RMSSD, LF, HF, and TP) were significantly lower after the operation than before the operation in both the laparoscopic and open groups (P < 0.05). The postoperative reduction in RMSSD and HF was significantly higher in the laparoscopic group than in the open group (P < 0.05). Conclusions: These data suggest that radical hysterectomy can lead to increased heart rate and decreased HRV in patients with ECC, which can negatively affect cardiac autonomic regulation. Compared with open surgery, laparoscopic surgery has a greater negative impact on the HRV of ECC patients.
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BACKGROUND: The aim of this prospective study was to evaluate the association between heart rate variability (HRV) and overall survival of lung cancer patients with brain metastases (LCBM). METHODS: Fifty-six LCBM patients were enrolled in this study. Five-minute electrocardiograms were collected before the time to first brain radiotherapy. HRV was analyzed quantitatively by using the time domain parameters, i.e., the standard deviation of all normal-normal intervals (SDNN) and the root mean square of successive differences (RMSSD). Survival time for LCBM patients was defined as from the date of HRV testing to the date of death or the last follow-up. RESULTS: In the univariate analysis, SDNN ≤ 13 ms (P = 0.003) and RMSSD ≤ 4.8 ms (P = 0.014) significantly predicted poor survival. Multivariate analysis confirmed that RMSSD ≤ 4.8 ms (P = 0.013, hazard ratio = 3.457, 95% confidence interval = 1.303-9.171) was also an independent negative prognostic factor after adjusting for mean heart rate, Karnofsky performance status, and number of brain metastases in LCBM patients. CONCLUSION: Decreased RMSSD is independently associated with shorter survival time in LCBM patients. HRV might be a novel predictive biomarker for LCBM prognosis.
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PURPOSE: Heart rate variability (HRV) has been reported as a useful biomarker for prognostic factors in a variety of cancers. The purpose of this study was to explore the predictive value of preoperative HRV for lymph node metastasis (LNM) in patients with cervical cancer (CC). PATIENTS AND METHODS: A total of 77 patients with CC were included, including 18 LNM and 59 non-LNM patients. A five-minute resting electrocardiogram (ECG) was collected before surgery for the analysis of HRV time domain, frequency domain and Poincaré plot parameters (ie, SDNN, RMSSD, LF, HF, LF/HF, SD1, SD2 and SD2/SD1). Student's t-tests and logistic regression were performed to determine the relationship between HRV and LNM. RESULTS: The LNM group had significantly lower SDNN, LF, and SD2 than the non-LNM group (all p < 0.05; all Cohen's d > 0.5). Binary logistic regression analysis indicated that SDNN, LF and SD2 were still significantly associated with LNM. Specifically, for each 1 ms decrease in SDNN and SD2 and each 1 logarithmic unit decrease in ln (LF), the odds of LNM increased by 12%, 9%, and 86%, respectively (all p < 0.05). CONCLUSION: These findings suggest an association between HRV and CC LNM, and HRV could be a potential noninvasive biomarker for the prediction of LNM in CC patients.
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Blood inflammatory biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), the lymphocyte-to-monocyte ratio (LMR), and the platelet-to-lymphocyte ratio (PLR), play a significant role in determining the prognosis of patients with cervical cancer (CC). Currently, no methods are available to predict these indexes pre-operatively. Cardiac autonomic function is determined based on the heart rate variability (HRV), which is also associated with a progressive inflammatory response and cancer. Thus, the main aim of this study was to evaluate the feasibility of using pre-operative HRV parameters in CC patients to predict post-operative blood inflammation biomarkers as a means of determining prognosis. Between 2020 and 2021, 56 patients who were diagnosed with CC and then underwent hysterectomy surgery at the Department of Gynecologic Oncology, First Affiliated Hospital, Bengbu Medical College were enrolled in this study. Five-minute electrocardiogram data were collected 1 day before the operation for analysis of HRV parameters, including frequency domain parameters (LF, HF, and LF/HF) and Poincaré plot parameters (SD1, SD2, and SD2/SD1). Venous blood was collected 2 days post-operatively and inflammatory biomarkers were evaluated, with the NLR, LMR, and PLR determined. Pre-operative SD2 was significantly associated with post-operative PLR, with each 1-unit increase in SD2 decreasing the PLR value by 2.4 ± 0.9 (P < 0.05). Besides, LF/HF was significantly correlated with NLR, with each 1-unit increase in LF/HF increasing the NLR value by 1.1 ± 0.5 (P < 0.05). This association was independent of patient age and body mass index. These results suggest that the pre-operative autonomic nervous system plays a role in the regulation of post-operative cancer inflammation and that pre-operative HRV parameters can potentially predict post-operative inflammation and facilitate clinical treatment decisions.
